Drug Administration Process Research Articles

An Autoclavable Steerable Cannula Manual Deployment Device: Design and Accuracy Analysis.

Accessing a specific, predefined location identified in medical images is a common interventional task for biopsies and drug or therapy delivery. While conventional surgical needles provide little steerability, concentric tube continuum devices enable steering through curved trajectories. These devices are usually developed as robotic systems. However, manual actuation of concentric tube devices is particularly useful for initial transfer into the clinic since the Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval process of manually operated devices is simple compared to their motorized counterparts. In this paper, we present a manual actuation device for the deployment of steerable cannulas. The design focuses on compactness, modularity, usability, and sterilizability. Further, the kinematic mapping from joint space to Cartesian space is detailed for an example concentric tube device. Assessment of the device's accuracy was performed in free space, as well as in an image-guided surgery setting, using tracked 2D ultrasound.

Monitoring of a protocol for the adequacy of the pharmaceutical form of the oral medication to the degree of dysphagia in patients hospitalized in an internal medicine service

The oral route is the most convenient way of administering medication, although it may not be safe. Dysphagia is one of the factors rendering difficult a proper feeding and administration of medication. to improve the administration of oral medication in patients with dysphagia by changing the pharmaceutical formulation of the principles prescribed to tolerable textures. Pilot project for the application of a dysphagia protocol that included the patients admitted to the Internal Medicine Unit at Los Montalvos Center for 4 months. After detecting the suspicion of dysphagia, a dysphagia-viscosity test was applied to know the tolerated textures. Then, the pharmaceutical formulations were adapted and the manipulation instructions for the drugs were indicated for their proper administration. 23 out of 627 admitted patients were included, with a mean age of 85 years (σ±7.4). The pathologies implicated in dysphagia were: dementia (65.2%); cerebrovascular disease (30.4%), and Parkinson's disease (4.4%). The best texture for drug intake was a "pudding" in 48.0%. 43 active ingredients were reviewed and 134 interventions were performed: in 41% of the cases, swallowing was made easier by mixing the drug with the food and in 59% water and a thickener were used. 94% of the recommendations were considered to be appropriate. the adaptation of the pharmaceutical formulations to the degree of dysphagia impacts on the improvement of healthcare quality by implementing safety in drug prescription and administration processes.

Exploring the delivery of antiretroviral therapy for symptomatic HIV in Swaziland: threats to the successful treatment and safety of outpatients attending regional and district clinics

AimTo examine the safety and acceptability of providing antiretroviral therapy (ART) in a resource poor setting.DesignTwo-stage observational and qualitative study.SettingRural hospital in Southern Africa.MethodsStructured observation using failure modes and effects...

A comprehensive RFID solution to enhance inpatient medication safety

Errors involving medication administration can be costly, both in financial and in human terms. Indeed, there is much potential for errors due to the complexity of the medication administration process. Nurses are often singled out as the only responsible of these errors because they are in charge of drug administration. Nevertheless, the interventions of every actor involved in the process and the system design itself contribute to errors (Wakefield et al. (1998) [23]). Proper inpatient medication safety systems can help to reduce such errors in hospitals. In this paper, we review in depth two recent proposals (Chien et al. (2010) [7]; Huang and Ku (2009) [12]) that pursue the aforementioned objective. Unfortunately, they fail in their attempt mainly due to their security faults but interesting ideas can be drawn from both. These security faults refer to impersonation and replay attacks that could produce the generation of a forged proof stating that certain medication was administered to an inpatient when it was not. We propose a leading-edge solution to enhance inpatient medication safety based on RFID technology that overcomes these weaknesses. Our solution, named Inpatient Safety RFID system (IS-RFID), takes into account the Information Technology (IT) infrastructure of a hospital and covers every phase of the drug administration process. From a practical perspective, our system can be easily integrated within hospital IT infrastructures, has a moderate cost, is very ease to use and deals with security aspects as a key point.

Use of Generic Antiretroviral Agents and Cost Savings in PEPFAR Treatment Programs

One of the biggest hurdles to the rapid scale-up of antiretroviral therapy in the developing world was the price of antiretroviral drugs (ARVs). Modification of an existing US Food and Drug Administration (FDA) process to expedite review and approval of generic ARVs quickly resulted in a large number of FDA-tentatively approved ARVs available for use by the US President's Emergency Plan for AIDS Relief (PEPFAR). To evaluate the uptake of generic ARVs among PEPFAR-supported programs in Guyana, Haiti, Vietnam, and 13 countries in Africa, and changes over time in ARV use and costs. An annual survey from 2005 to 2008 of ARVs purchased in 16 countries by PEPFAR implementing and procurement partners (organizations using PEPFAR funding to purchase ARVs). Drug expenditures, ARV types and volumes (assessed per pack, a 1-month supply), proportion of generic procurement across years and countries, and cost savings from generic procurement. ARV expenditures increased from $116.8 million (2005) to $202.2 million (2008); and procurement increased from 6.2 million to 22.1 million monthly packs. The proportion spent on generic ARVs increased from 9.17% (95% confidence interval [CI], 9.17%-9.18%) in 2005 to 76.41% (95% CI, 76.41%-76.42%) in 2008 (P < .001), and the proportion of generic packs procured increased from 14.8% (95% CI, 14.79%-14.84%) in 2005 to 89.33% (95% CI, 89.32%-89.34%) in 2008 (P < .001). In 2008, there were 8 PEPFAR programs that procured at least 90.0% of ARV packs in generic form; South Africa had the lowest generic procurement (24.7%; 95% CI, 24.6%-24.8%). Procurement of generic fixed-dose combinations increased from 33.3% (95% CI, 33.24%-33.43%) in 2005 to 42.73% (95% CI, 42.71%-42.75%) in 2008. Estimated yearly savings generated through generic ARV use were $8,108,444 in 2005, $24,940,014 in 2006, $75,645,816 in 2007, and $214,648,982 in 2008, a total estimated savings of $323,343,256. Among PEPFAR-supported programs in 16 countries, availability of generic ARVs was associated with increased ARV procurement and substantial estimated cost savings.

Non‐therapeutic omission of medications in acutely ill patients

To examine documentation of medication administration in medical and surgical patients. (1) Determine the point prevalence of non-therapeutic medication omissions; (2) identify documented reasons for non-therapeutic medication omissions; (3) examine the relationship between length of stay and medication omissions; and (4) explore the impact of outlier status (e.g. medical patients managed on surgical wards) on medication administration. Acutely ill patients are particularly sensitive to health care errors. We previously identified a 26% rate of non-therapeutic medication omissions in patients admitted unexpectedly to intensive care unit (ICU) from medical and surgical wards. A point prevalence survey of 162 medical and surgical patients across four sites in the South West of England. Data collected included: all instances of, and reasons for, non-therapeutic medication omission. We also recorded whether the patient was an 'outlier' and examined nursing documentation where no reason for medication omission was given on the drug chart. The number of patients who missed at least one medication was high across all sites (n = 129/162; 79.6%, range 60-88%), with a total of 1077 doses omitted. Patients who were outliers (e.g. surgical patients on a medical ward) were more likely to miss medications (100% versus 74%, p < 0.001). The most common missed medications were analgesia and anti-inflammatory drugs (28%, 299/1077); 203 of these were due to patient refusal. The extent of medications omitted for non-therapeutic reasons in medical and surgical patients is of concern. None were recorded as an adverse drug event; however, the extent of omitted or refused medications suggests the need for a review of prescribing and drug administration processes. These findings have important implications for the role of ICU outreach and liaison services, for example, including medication management in the monitoring of patients pre/post-ICU admission and support/education provided for ward staff. Detailed analysis of medication records suggests a number of areas of medication administration that would benefit from review.

Considerations for Tissue-Engineered and Regenerative Medicine Product Development Prior to Clinical Trials in the United States

Tissue-engineered and regenerative medicine products are promising innovative therapies that can address unmet clinical needs. These products are often combinations of cells, scaffolds, and other factors and are complex in both structure and function. Their complexity introduces challenges for product developers to establish novel manufacturing and characterization techniques to ensure that these products are safe and effective prior to clinical trials in humans. Although there are only a few commercial products that are currently in the market, many more tissue-engineered and regenerative medicine products are under development. Therefore, it is the purpose of this article to help product developers in the early stages of product development by providing insight into the Food and Drug Administration (FDA) process and by highlighting some of the key scientific considerations that may be applicable to their products. We provide resources that are publically available from the FDA and others that are of potential interest. As the provided information is general in content, product developers should contact the FDA for feedback regarding their specific products. Also described are ways through which product developers can informally and formally interact with the FDA early in the development process to help in the efficient progression of products toward clinical trials.

Practitioners need corporate compliance education: AAO–HNS survey results

The environment in which otolaryngologists coexist with device and drug development has become increasingly complex. There are broad implications for both the academic and the private practitioner, with neither group being more or less insulated than the other. From the medical, ethical, and resource-oriented standpoints, otolaryngologists must consider this evolving area very carefully. A survey of the American Association of Otolaryngology–Head and Neck Surgery membership identified areas of education to improve the awareness and knowledge base of these complex considerations. In particular, knowledge of legal proceedings, Food and Drug Administration processes, relevant hospital resources, and conflict of interest considerations were areas in which the membership would benefit from further instruction.

Lung Water

Newspaper headlines have greeted with circumspection the report from the Government Accountability Office on the United States Food and Drug Administration (FDA) processes to regulate medical devices. They used sentences such as “Left to the FDA’s own devices” 1 and “Is That Device Safe?” 2. Such headlines bring attention to the fact that FDA requirements for approval and clearance of medical devices are markedly different from those for drugs3, 4. Most new devices are cleared, not approved, through the premarket notification (510(k)) pathway. This is a FDA process based on the assumption that the majority of new devices are essentially equivalent to those already approved. Physiological monitors are usually among these, and frequently enter the market due to their substantial equivalence to previous models, with limited scrutiny of efficacy 3, 4. Thus, as new monitors are introduced, it is crucial for good clinical practice to understand their principles, advantages and limitations. In this issue of Anesthesiology, Easley et al.5 apply functional lung imaging techniques to study measurements of extravascular lung water (EVLW) using the single indicator (iced saline) transpulmonary thermodilution method. The device was recently cleared by the FDA (PiCCO, Pulsion Medical Systems, Munich, Germany).

For the record

The United States Food and Drug Administration's process for approving high-risk class III medical devices is outdated and fails to ensure the safety and effectiveness of such products, according to a report by the highly respected US Government Accountability Office, ([www.gao.gov/new.items/d09190.

Confidence and competence in paediatric drug calculations

Nurse prescibers have a unique role for many reasons, one of which being that they, unlike other prescribing professionals, may be responsible for more than one stage of the drug administration process. They are one of the few groups of clinicians who may prescribe, dispense and administer drugs to their patient, and on occasion may perform more than one of these roles. This holistic function is one of the joys of the autonomous advanced practice role, yet without ensuring that adequate provision is made for patient safety and risk assessment, this fluid procedure also leads to greater vulnerability for the practitioner and the service user, when considering the potential for medication error. This risk is increased if the individual prescriber is not confident in his/her ability to perform drug calculations, particularly in relation to another susceptible group, namely babies and children.

Combined wavelet transform–artificial neural network use in tablet active content determination by near-infrared spectroscopy

The pharmaceutical industry faces increasing regulatory pressure to optimize quality control. Content uniformity is a basic release test for solid dosage forms. To accelerate test throughput and comply with the Food and Drug Administration's process analytical technology initiative, attention is increasingly turning to nondestructive spectroscopic techniques, notably near-infrared (NIR) spectroscopy (NIRS). However, validation of NIRS using requisite linearity and standard error of prediction (SEP) criteria remains a challenge. This study applied wavelet transformation of the NIR spectra of a commercial tablet to build a model using conventional partial least squares (PLS) regression and an artificial neural network (ANN). Wavelet coefficients in the PLS and ANN models reduced SEP by up to 60% compared to PLS models using mathematical spectra pretreatment. ANN modeling yielded high-linearity calibration and a correlation coefficient exceeding 0.996.

Transient gene expression in CHO cells monitored with automated flow cytometry

Transient gene expression is frequently used in industry to rapidly generate usable quantities of a protein from cultured cells. In gene therapy applications it is used to express a therapeutic protein in vivo. A quantitative assessment of the expression kinetics is important because it enables optimization and control of culture conditions for higher productivity. Previous experimental studies show a characteristic peak in average protein expression per cell after transfection followed by an exponential decrease of the expressed protein. Here, we show that the exponential decrease in single cell expression of enhanced Green Fluorescent Protein (eGfp) occurs in discrete steps. We attribute this to the absence of plasmid replication and to symmetric partitioning of plasmid and eGfp between dividing cells. This is reflected in the total eGfp in the bioreactor, which increased at a constant rate throughout the experiment. Additionally, the data provide a detailed time course of cell physiology during recovery from electroporation. The time course of cell physiology precisely indicates when the culture shifts growth phases. Furthermore, the data indicate two unique stationary phases. One type of stationary phase occurs when proliferation ceases while cells decrease their cell size, maintain granularity, and mean eGfp content decreases. The second type occurs when proliferation ceases while cells increase their cell size, increase granularity, and surprisingly maintain eGfp content. The collected data demonstrate the utility of automated flow cytometry for unique bioreactor monitoring and control capabilities in accordance with the US Food and Drug Administration's Process Analytical Technology initiative.

A Standardized Approach to Pediatric Parenteral Medication Delivery

Delivering medications safely to hospitalized pediatric patients presents a significant challenge. Current JCAHO standards require safe medication practices, including the standardization of parenteral medications and solutions. Our institution convened a pediatric process improvement team (consisting of pharmacists, nurses, physicians, and administrators) to address deficiencies in our medication use process. This article describes the standardized parenteral medication processes that this committee ultimately endorsed. The new system was designed to control, simplify, and standardize each major step in the medication use process, from prescribing through administration. The system involved defining and standardizing prescribing practices, which then allowed for reduced variability and the preplanning of drug preparation and administration processes. To ease transition and simplify implementation, three phases of the process were introduced in a step-by-step manner: phase 1, continuous infusions; phase 2, intermittent IV doses; and phase 3, bulk IV fluids. Time to implementation included 6 months of preparation prior to phases 1 and 2 and approximately another year to phase 3. The standardized pediatric parenteral medication process has resulted in improved patient safety and operational efficiency. It has also eliminated the “Rule of six” method of drug preparation and administration.

Controlling Bleeding in the Field: Hemostatic Powders and Dressings Debut in the Prehospital Setting

While Americans continue to debate the war on Iraq, battlefield personnel are exploring several technologies that are currently making their way through the Food and Drug Administration (FDA) process to the streets at home for treatment of patients with severe bleeding. These “hemostatins” seek to achieve the same effect with different materials and in different ways. Some add coagulants at the wound site; others constrict bleeding arteries near the wound and activate platelets to stop bleeding. Their efficacy has been studied with animal models,1 and they are now being used in clinical settings.

A Peek into Pandora's Box

The smoking of marijuana for medicinal applications is a volatile and difficult issue for the medical and regulatory communities which has reached the forefront of discussions of public policy. Any consideration of this issue must take into account the substantial toxicity, impurity, and morbidity associated with marijuana use. Several states have passed ballot initiatives or legislation that allow a medical excuse for possession of marijuana. These initiatives bypass the Food and Drug Administration process of proving safety and efficacy, and they have created serious regulatory dilemmas for state regulatory boards. Several examinations of the issue have consistently drawn question to the validity of smoking an impure substance while voicing concern for the well being of patients in need. The historical, social, medical, and legal issues are examined.

Applications of process analytical technology to crystallization processes

Crystallizations of pharmaceutical active ingredients, particularly those that posses multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. The Food and Drug Administration's process analytical technology (PAT) initiative is a collaborative effort with industry to introduce new and efficient manufacturing technologies into the pharmaceutical industry. PAT's are systems for design, analysis, and control of manufacturing processes. They aim to assure high quality through timely measurements of critical quality and performance attributes of raw materials, in-process materials, and final products. Implementation of PAT involves scientifically based process design and optimization, appropriate sensor technologies, statistical and information tools (chemometrics), and feedback process control strategies working together to produce quality products. This review introduces the concept of PAT and discusses its application to crystallization processes through review of several case studies. A variety of in situ analytical methods combined with chemometric tools for analysis of multivariate process information provide a basis for future improvements in modeling, simulation, and control of crystallization processes.

Batch And Continuous Processing In The Production Of Pharmaceutical Granules

A quasicontinuous granulation and drying process to avoid scale-up problems is introduced in this work. Consistent and reproducible granule quality is a key factor in robust dosage form design and fits ideally the prerequisites of a drug quality system for the twenty-first century and the Food and Drug Administration's Process Analytical Technology (PAT) initiative. In scale-up, factors that simulate or reproduce the laboratory scale must be considered. This system provides a new possibility for industrial manufacturing and galenical development of pharmaceutical solids. The quasicontinuous method described in the present work, and the laboratory and production batches and the granulating equipment used to produce them, are the same. Once a robust process has been defined in the laboratory, it is merely repeated as many times as necessary to achieve the desired final batch size. The quasicontinuous process gives new possibilities to simplify manufacturing procedures and to validate them faster. The quality of the resulting granules and tablets compared with classical methods is equal until better. In many cases, existing products have been transferred to the multicell process without formulation changes. The quasicontinuous production concept for high-shear granulation and fluid-bed drying offers many advantages over the classical methods used to produce pharmaceutical granules. The wet massing process may be monitored by the power consumption of the mixer motor for each subunit, as in classical high-shear granulation processes. The air volume, temperature, and humidity of each of the drying cells may be controlled individually to avoid overheating of temperature-sensitive materials. All processing variables must be precisely controlled by a computer, and the data must be collected for documentation. As such, product quality and reproducibility for each subunit is assured.

Reengineering intravenous drug and fluid administration processes in the operating room: step one: task analysis of existing processes.

A reengineering approach to intravenous drug and fluid administration processes could improve anesthesia care. In this initial study, current intravenous administration tasks were examined to identify opportunities for improved design. After institutional review board approval was obtained, an observer sat in the operating room and categorized, in real time, anesthesia providers' activities during 35 cases ( approximately 90 h) into 66 task categories focused on drug/fluid tasks. Both initial room set-up at the beginning of a typical workday and cardiac and noncardiac general anesthesia cases were studied. User errors and inefficiencies were noted. The time required to prepare de novo a syringe containing a mock emergency drug was measured using a standard protocol. Drug/fluid tasks consumed almost 50 and 75%, respectively, of the set-up time for noncardiac and cardiac cases. In 8 cardiac anesthetics, drug/fluid tasks comprised 27 +/- 6% (mean +/- SD) of all prebypass clinical activities. During 20 noncardiac cases, drug/fluid tasks comprised 20 +/- 8% of induction and 15 +/- 7% of maintenance. Drug preparation far outweighed drug administration tasks. Inefficient or error prone tasks were observed during drug/fluid preparation (e.g., supply acquisition, waste disposal, syringe labeling), administration (infusion device failure, leaking stopcock), and organization (workspace organization and navigation, untangling of intravenous lines). Anesthesia providers (n = 21) required 35 +/- 5 s to prepare a mock emergency drug. Intravenous drug and fluid administration tasks account for a significant proportion of anesthesia care, especially in complex cases. Current processes are inefficient and may predispose to medical error. There appears to be substantial opportunity to improve quality and cost of care through the reengineering of anesthesia intravenous drug and fluid administration processes. General design requirements are proposed.

Preventing Medication Errors with Antineoplastic Agents, Part 2

Goal The goal of this program is to present practical ways to prevent medication errors with antineoplastic agents, identify common types of medication errors, and describe a system for reducing and responding appropriately to antineoplastic medication errors. Objectives At the completion of this program the participant will be able to: 1. Describe the scope and impact of medication errors 2. Define common terms used in medication error literature. 3. List four common types of prescribing errors made with antineoplastic agents. 4. Identify steps where medication errors may occur in the drug ordering, preparation, and administration process. 5. Describe ways to prevent errors at each step of the medication use process. 6. Recommend a procedure for reporting and monitoring antineoplastic medication errors within the institution. 7. Describe a system for the nonpunitive management of antineoplastic medication errors in health care systems.