Application of Near-Infrared Spectroscopy for Screening of Chlorothiazide Sodium Vials.

Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO2) is vital, with measurements ranging from 0.417×10-5 to 1.012×10-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO2 boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.

Screening for quality with process analytical technology in a health-system pharmacy: A primer.

PURPOSE: The University of Kentucky Drug Quality Study team briefly reviews the growing concerns over pharmaceutical manufacturing quality in the globalized environment, reviews the historical approach by the US Food and Drug Administration (FDA) that prioritizes process over product in enforcing quality with manufacturers, reviews the science of process analytical technology (PAT) such as near-infrared (NIR) spectroscopy, illustrates the use of PAT methods for assessing uniformity and quality in injectable pharmaceuticals, and demonstrates the application of NIR spectroscopy in a health-system pharmacy setting while maintaining current good practice quality guidelines and regulations (cGxP). SUMMARY: Given that the current approach to monitoring quality in pharmaceutical manufacturing was developed in the late 1960s at a time when manufacturing was mostly domestic, the current approach prioritizes process over product, and the global footprint of manufacturing is straining federal resources to fulfill their task of monitoring quality, an approach to augment the quality monitoring process has been developed. PAT methodologies are supported by FDA for monitoring quality and offer a fast, low-cost, nondestructive solution. Given that the Accreditation Council for Pharmacy Education has not required qualitative/quantitative analysis and drug assaying in the pharmacy curriculum for several decades, the authors spend time explaining the science behind one of these PAT methodologies, NIR spectroscopy. This primer reviews the application of this technology in the health-system pharmacy setting and the relevant clinical applications. CONCLUSION: Utilizing PAT methodologies such as NIR spectroscopy, health-system pharmacies can gain insights about whether process controls are in place or lacking in FDA-approved formulations.

Assessment of Vecuronium Quality Using Near-Infrared Spectrometry.

This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.

FDA Approaches in Monitoring Drug Quality, Forces Impacting the Drug Quality, and Recent Alternative Strategies to Assess Quality in the US Drug Supply.

Since the US Food and Drug Administration (FDA) began monitoring the quality of pharmaceutical manufacturing by enforcing current good manufacturing practices roughly 60 years ago, forces related to the global economy have changed, rendering the task of monitoring quality more difficult. Alternative strategies by groups like Valisure, LLC, and the University of Kentucky Drug Quality Study to monitor the quality of the currently circulated US drug supply through end-product testing and screening have resulted in several concerning findings. Given the successful approaches of identifying quality defects in pharmaceuticals by non-regulatory bodies, and considering the changing landscape and pressures on manufacturing, the FDA, large buying groups, and the US Department of Defense should consider these alternative strategies as a means to augment current regulatory activities.

Implementation of a prioritized scoring tool to improve time to pharmacist intervention.

PURPOSE: The implementation of a prioritized scoring tool to improve time to pharmacist intervention is described. SUMMARY: At the Ohio State University Wexner Medical Center, pharmacists are accepted providers of therapeutic drug monitoring of vancomycin and aminoglycosides. At the onset of this initiative and despite the implementation of an integrated electronic medical record (EMR), management of pharmacokinetically monitored medications was conducted using a paper monitoring form. The potential for transcription errors during this process provided an opportunity for improvement. For these reasons, the department of pharmacy focused its initial efforts for a patient scoring system on the pharmacokinetics scoring module. Adjustment of associated medications based on pharmacokinetic values was a core function of pharmacists of the institution and was expected to be conducted without fail. Vancomycin was used as the index surrogate pharmacokinetically monitored medication within the module for testing and validation because of the clear expectations and standardized resources available to pharmacists to complete the task. The pharmacokinetics scoring module was designed specifically for the function of dosing management, searching throughout the EMR and concisely displaying the information a pharmacist needs to make a clinical decision. Importantly, integration of the scoring module reduced the time to intervention from hours to minutes. The median time to intervention was reduced to within a clinical working shift (8 hours) with the scoring module versus 24 hours or longer with the paper monitoring system. CONCLUSION: The implementation of an internally developed pharmacokinetics scoring module built into the EMR substantially reduced the time to clinical intervention for pharmacokinetic monitoring of vancomycin drug levels.

Critical Care Pharmacist Market Perceptions: Comparison of Critical Care Program Directors and Directors of Pharmacy.

Background: While hospital beds continue to decline as patients previously treated as inpatients are stabilized in ambulatory settings, the number of critical care beds available in the United States continues to rise. Growth in pharmacy student graduation, postgraduate year 2 critical care (PGY2 CC) residency programs, and positions has also increased. There is a perception that the critical care trained pharmacist market is saturated, yet this has not been evaluated since the rise in pharmacy graduates and residency programs. Purpose: To describe the current perception of critical care residency program directors (CC RPDs) and directors of pharmacy (DOPs) on the critical care pharmacist job market and to evaluate critical care postresidency placement and anticipated changes in PGY2 CC programs. Methods: Two electronic surveys were distributed from October 2015 to November 2015 through Vizient/University HealthSystem Consortium, American Society of Health-System Pharmacists (ASHP), Society of Critical Care Medicine, and American College of Clinical Pharmacy listservs to target 2 groups of respondents: CC RPDs and DOPs. Questions were based on the ASHP Pharmacy Forecast and the Pharmacy Workforce Center's Aggregate Demand Index and were intended to identify perceptions of the critical care market of the 2 groups. Results: Of 116 CC RPDs, there were 66 respondents (56.9% response rate). Respondents have observed an increase in applicants; however, they do not anticipate increasing the number of positions in the next 5 years. The overall perception is that there is a balance in supply and demand in the critical care trained pharmacist market. A total of 82 DOPs responded to the survey. Turnover of critical care pharmacists within respondent organizations is expected to be low. Although a majority of DOPs plan to expand residency training positions, only 9% expect to increase positions in critical care PGY2 training. Overall, DOP respondents indicated a balance of supply and demand in the critical care trained pharmacist market. In comparing RPD and DOP perceptions of the demand for critical care pharmacists, DOPs perceived demand to be higher than RPDs (mean, 3.2 vs 2.8; P = .032). Conclusion: Although there is a perception of the oversupply of critical care trained pharmacists, a survey of DOPs and CC RPDs found a market with positions available, rapid hiring, stable salaries, and plans for expanded hiring of critical care trained pharmacists.

Evolving Pharmacist Productivity Models.

Leaders in health-system pharmacy are challenged to minimize costs, maximize revenue, and maintain or improve quality while simultaneously expanding services. Strong command of productivity and workload measurement is necessary to achieve these goals. This article reviews foundational pharmacy productivity concepts and key terminology, reviews historical pharmacy productivity models and their limitations, and considers new and evolving pharmacist productivity models.

An evaluation of acuity adjustment metrics to track medication expense over time.

PURPOSE: The acuity adjustment metric that correlates most closely with actual medication expense at a large, tertiary care academic medical center was investigated. METHODS: This evaluation was conducted at the Ohio State University Wexner Medical Center. All inpatient discharges between July 1, 2012, and March 31, 2013, were included in this study. Patient medical and financial records were used to obtain the diagnosis-related group (DRG) codes and total medication cost for each patient discharge. The primary DRG for each patient was then used to assign the corresponding relative weight (RW) and pharmacy intensity weight (PIW). The correlation between actual and predicted medication expenditure was determined for every DRG for both RW and PIW. Since this compares cost at the DRG level, RW and PIW were used as markers for case-mix index (CMI) and pharmacy intensity score (PIS), respectively. RESULTS: At this single institution, medication cost per discharge was more strongly correlated with PIW (as a marker for PIS) than with RW (as a marker for CMI). Extrapolating these data to hospital-specific values, the results suggest that PIS is more strongly correlated with overall medication expense than CMI and therefore a better adjustment metric for monitoring medication expense over time. CONCLUSION: A single-institution study demonstrated that PIW was more strongly correlated than RW with actual medication expenditure. PIS may be a more accurate acuity metric than CMI for predicting changes in drug expense over time.

Development of an inpatient operational pharmacy productivity model.

PURPOSE: An innovative model for measuring the operational productivity of medication order management in inpatient settings is described. METHODS: Order verification within a computerized prescriber order-entry system was chosen as the pharmacy workload driver. To account for inherent variability in the tasks involved in processing different types of orders, pharmaceutical products were grouped by class, and each class was assigned a time standard, or "medication complexity weight" reflecting the intensity of pharmacist and technician activities (verification of drug indication, verification of appropriate dosing, adverse-event prevention and monitoring, medication preparation, product checking, product delivery, returns processing, nurse/provider education, and problem-order resolution). The resulting "weighted verifications" (WV) model allows productivity monitoring by job function (pharmacist versus technician) to guide hiring and staffing decisions. A 9-month historical sample of verified medication orders was analyzed using the WV model, and the calculations were compared with values derived from two established models­one based on the Case Mix Index (CMI) and the other based on the proprietary Pharmacy Intensity Score (PIS). RESULTS: Evaluation of Pearson correlation coefficients indicated that values calculated using the WV model were highly correlated with those derived from the CMI-and PIS-based models (r = 0.845 and 0.886, respectively). Relative to the comparator models, the WV model offered the advantage of less period-to-period variability. CONCLUSION: The WV model yielded productivity data that correlated closely with values calculated using two validated workload management models. The model may be used as an alternative measure of pharmacy operational productivity.