Handling Of Hazardous Drugs Research Articles

Quality Assurance in Safe Handling of Hazardous Drugs Among Healthcare Workers in KSA: A Scoping Review

Healthcare providers are potentially at risk from occupational exposure to drugs. Safe handling accreditation criteria from international occupational safety organizations and associations minimize long-term medication exposure harm. The purpose of this review was to examine healthcare workers' quality assurance in the safe handling of hazardous drugs. This topic underwent a scoping review of the literature to determine what was known about exposure and to spot any knowledge gaps using a variety of electronic databases such as Medline, PubMed, EMBASE, Web of Science, and Google Scholar for the literature search. English-language articles that were published between 1997 and 2022 were included. This review included 26 full-text papers in total. The designs, sample sizes, sample collection durations, and medicines studied differed between the investigations. Numerous studies discovered that at least one sample had measurable quantities of a hazardous substance. The studies examined that hazardous drugs are handled in many different stages throughout the healthcare industry, including production, transportation, storage, preparation for patients, and waste disposal after treatment. Healthcare personnel are constantly exposed to HDs. The findings emphasize the need to establish robust regulations, boost training programs, upgrade personal protective equipment, enhance handling techniques, and strengthen monitoring and surveillance systems. More research is required to fill up the gaps and safeguard the safety and health of Saudi Arabia's healthcare professionals who handle hazardous medications.

National survey of safe handling of hazardous drugs in hospital settings: Use of an innovative approach.

Workers can reduce their risk of exposure to hazardous drugs by following safe handling guidelines. Healthcare centers need to dedicate time and resources in order to implement new safety recommendations. The objective was to present the results of a national survey about the safe handling of hazardous drugs in healthcare centers. Quebec healthcare centers performed an auto-evaluation to the newly updated safe handling guidelines in 2021. Centers rated each criterion as compliant or non-compliant. The guidelines tailored recommendations according to three categories of hazards: G1, consisting mostly of carcinogenic drugs; G2, other hazardous drugs; and G3, those with reproductive toxicity. The questionnaire prompted participants to document their planned corrective measures for non-compliant criteria. Most centers participated (28/29, 97%). The overall compliance was 58% (8761/15,216 criteria). The conformity per theme was hygiene and sanitation (1290/1,878, 69%), laundry (221/367, 60%), pharmacy (2658/4,474, 59%), nursing (3436/6,017, 57%), spills and accidental exposure (353/649, 54%), and general measures (803/1,831, 44%). It was higher for recommendations regarding G1s (4226/6,115, 69%) than for G2s (1626/3557, 46%) and G3s (372/916, 41%). This project successfully used an innovative approach that combined a national auto-evaluation survey, an actionable report, and the involvement of a community of practice. Centers were able to benchmark their implementation of safe handling guidelines, and community of practices may help in sharing the best practices. The design of the questionnaire helped in targeting corrective measures. More work is needed for safe handling practices that relate to G2 and G3 drugs.

Safe procedure development to manage hazardous drugs in the workplace

ObjectiveTo develop a safety working procedure for the employees in the Intermutual Hospital de Levante (HIL) in those areas of activity that deal with the handling of hazardous drugs (MP). MethodsThe procedure was developed in six phases: 1) hazard definition; 2) definition and identification of processes and development of general correct work practices about hazardous drugs’ selection and special handling; 3) detection, selection and set of specific recommendations to handle with hazardous drugs during the processes of preparation and administration included in the hospital GFT; 4) categorization of risk during the preparation/administration and development of an identification system; 5) information and training of professionals; 6) implementation of the identification measures and prevention guidelines. ResultsSix processes were detected handling HD. During those processes, thirty HD were identified included in the hospital GFT and a safer alternative was found for 6 of them. The HD were classified into 4 risk categories based on those measures to be taken during the preparation and administration of each of them. ConclusionsThe development and implementation of specific safety-work processes dealing with medication handling, allows hospital managers to accomplish effectively with their legal obligations about the area of prevention and provides healthcare professional staff with the adequate techniques and safety equipment to avoid possible dangers and risks of some drugs.

1010: IMPACT OF USP-800 ON ADMINISTRATION TIMES OF HAZARDOUS INTRAVENOUS ANTIEPILEPTIC MEDICATIONS

Introduction: USP general chapter < 800> establishes comprehensive guidelines for safe handling of hazardous drugs, including some antiepileptics, by healthcare personnel. This guidance increases the number of steps required to safely compound and deliver medications, potentially resulting in a delay of care for time-sensitive medications. The aim of this study is to assess the impact that implementation of USP < 800> had on the timeliness of administration of antiepileptic medications at an academic medical center. Methods: A single center, retrospective study of time from verification to administration pre- and post-USP < 800> implementation of adult one-time orders of intravenous (IV) fosphenytoin (FOS), phenytoin (PHT), and valproic acid (VPA) was conducted. The study period includes 10 months immediately prior to adoption of USP < 800> and five months post adoption. One-time orders were included if scheduled administration time was within 90 minutes of verification. The primary outcome was time in minutes from order verification to medication administration. Subgroup analyses compared the results based on method of medication delivery (pneumatic tube system (PTS) vs hand delivery) and if orders were designated as “STAT”. Results: A total of 248 orders met inclusion criteria: 33 FOS, 12 PHT, and 203 VPA, (pre: 176, post: 72). Time from verification to administration was 15 minutes longer in the post-implementation group for aggregate antiepileptic orders (54 [35-72] vs 69 [48-90], p=0.0013). This increase in time to administration post-implementation was comparable across each of the medications assessed. Subgroup analysis of orders marked as “STAT” showed a similar increase in median time to administration (43 [28-65] vs 56 [34-86], p=0.0406). There was no difference in time to administration comparing PTS to hand delivery (71 [46-109] vs 68 [51-88], p=0.6603). Conclusions: Implementation of USP < 800> increased the median time from order verification to administration for three hazardous IV antiepileptic medications. In patients with status epilepticus, a 15 minute delay could prolong time to seizure termination resulting in worse clinical outcomes. Institutions will need to develop alternative methods for compounding and delivery to ensure timely administration while maintaining safety.

Safe handling of hazardous drugs.

Background: This evidence-based practice guideline was developed to update and address new issues in the handling of hazardous drugs including being compliant with NAPRA (National Association of Pharmacy Regulatory Authorities) and USP 800 (United States Pharmacopeia) standards, the use of personal protective equipment and treatment in diverse settings including in the home setting. Methods: This guideline was developed from an adaptation and endorsement of existing guidelines and from three systematic reviews. Prior to publication, this guideline underwent a series of peer, patient, methodological and external reviews to gather feedback. All comments were addressed and the guideline was amended when required. This guideline applies to and is intended for all health care workers who may come into contact with hazardous drugs at any point in the medication circuit. Results: The recommendations represent a reasonable and practical set of procedures that the intended users of this guideline should implement to minimize the opportunity for accidental exposure. These recommendations are not limited to just the point of care, but cover the entire chain of handling of cytotoxics from the time they enter the institution until they leave in the patient or as waste. Conclusions: Decreasing the likelihood of accidental exposure to cytotoxic agents within the medication circuit is the main objective of this evidenced-based guideline. The recommendations differ slightly from previous guidelines due to new evidence.

Safe Handling of Antineoplastic Drugs During Allergy Diagnostic Workup and Desensitization: A Single Experience of the Allergy Department in a Tertiary Hospital

The increased use of antineoplastic drugs has been associated with a rising number of hypersensitivity reactions to these drugs, which has led to a growth in the demand for assistance from allergy services. The involvement of an allergist is essential to ensure that these patients with hypersensitivity reactions continue to be able to receive appropriate first-line treatment. Chemotherapy and biological agents have specific handling requirements and all the allergy departments involved in the diagnosis and therapeutic management of patients reacting to these drugs should find the means to guarantee safety. There are currently several guidelines on the safe handling of hazardous drugs for healthcare workers. However, specific recommendations are lacking for reducing occupational exposure in staff working in the allergy departments and managing these drugs for the diagnosis and management of hypersensitivity reactions. This review article focuses on the safe handling strategy of the allergy department in the Ramón y Cajal University Hospital and provides details of its implementation and experience over 10 years. This protocol could improve the knowledge of safe handling of antineoplastic drugs in allergy procedures.

Effects of Educational Interventions to Improve Safe Hazardous Drug Handling among Oncology Nurses: Systematic Review

Background: Oncology nurses are in the front line of handling Hazardous Drugs (HDs) in healthcare settings.It is crucial to minimize the cytotoxic effects of handling HDs among oncology nursesby following the safety standards practices, protocols, and guidelines. The purpose of this systematicreview is to identify the effects of educational interventions to reduce exposure of hazardous drugs andchemicals among oncology nurses.Methods: The review was performed following the Preferred Reporting Items for Systematic Reviewand Meta-Analysis (PRISMA) guidelines. The search protocol was conducted using PubMed\MEDLINE, CINAHL, and Google Scholar, for studies published between the periods of 2013to 2021.Nine articles were included in the systematic reviewConclusion: Severalinterventions were identified including web-based online courses, educationalmodules, applied safety protocols, demonstration and re-demonstration, videos, PowerPointpresentations, seminars, and workshops. Following up nurses after applying different educationalinterventions showed enhanced adherence to safe handling of HDs. Applied educational interventionshave been reported to improve self-efficacy, nursing performance, attitude, knowledge, and practiceof cytotoxic drug handling. A better compliance was reported on nurses’use of standard personalprotective equipment, safety protocol during administration, handling of body fluids, and respondingto spills of HDs.

Leveraging a multidisciplinary oversight committee to ensure USP and compliance at a Veterans Affairs health system.

Producing compounded sterile preparations (CSP) of the highest quality and ensuring safe hazardous drug handling are well-established priorities for pharmacy departments. Maintaining compliance with United States Pharmacopeia general chapters 797 and 800 (USP <797> and <800>) must also be a priority for health-system leadership. This report describes how a pharmacy-driven multidisciplinary committee was created to provide USP <797> and <800> oversight within a multicampus Veterans Affairs health system and the facility and safety outcomes achieved. The Veterans Health Administration required facilities to establish an oversight committee to ensure USP-compliant CSP procedures and the safe handling of hazardous drugs in all aspects of the medication-use process. Spearheaded by the pharmacy department, the VA Palo Alto Health Care System (VAPAHCS) chartered the CSP Advisory Committee to achieve this goal.The membership was composed of department heads in the areas of pharmacy, nursing, environmental management services, engineering, facility planning, safety, industrial hygiene, employee health, supply chain services, infection control, and quality management and the health system's director's office. The medication safety officer served as the executive secretary for the advisory committee and was responsible for agenda development, minutes, and coordinating timely follow-ups on action items; the VAPAHCS deputy director served as chair. Monthly meetings were conducted to receive updates on targeted sterile compounding and hazardous drug handling objectives: environmental controls and monitoring, compliance with regulatory requirements, staff competency, hazardous drug exposure event analyses, and development of well-defined health-system policy to guide practice. Taking a multidisciplinary approach to USP <797> and <800> compliance facilitated communications, created engagement, and ensured completion of action plans.

An assessment of oncology pharmacy educational needs among community pharmacists in Zimbabwe

Background: Oncology pharmacy is a specialty that is central to provision and use of anti-cancer medications. In Zimbabwe, pharmacists rely on a Bachelor of Pharmacy degree (B.Pharm.) and in-house training in the provision of oncology services. This study sought to assess knowledge, perceptions, current practices and prior education in oncology pharmacy among community pharmacists. Methods: A cross-sectional survey was carried out among pharmacists working in community pharmacies in Harare. Results: A response rate of 93.0% was achieved. The mean knowledge score was 4.0%. Up to 96.8% of pharmacists thought that prior training in oncology was inadequate. Only ten pharmacists in the sample actually dispensed chemotherapy regularly. Of these, none comprehensive measures for the safe handling of hazardous drugs. Conclusion: A B.Pharm. degree does not provide pharmacists with adequate scientific knowledge and competencies required for the provision of oncology pharmacy services. Structured educational programmes for pharmacists in oncology should be implemented.

Safe Handling of Hazardous Drugs in Home Infusion.

Chemotherapy agents used for cancer treatment are considered hazardous drugs (HDs). Guidelines and standards for handling HDs have been in place for several decades to protect oncology nurses working in hospitals and outpatient infusion areas. However, chemotherapy is frequently being administered in home settings, often by infusion nurses who do not necessarily have the requisite knowledge and training. Providing appropriate education for home infusion nurses is key to ensuring they are practicing in a manner that minimizes potential exposure to HDs.

Creation of a regional hazardous drug handling task force.

A regional task force of health-system pharmacy leaders was created to assist with successful adoption of United States Pharmacopeia (USP) general chapter <800>. A group of pharmacy leaders in the Kansas City region identified potential benefits to healthcare personnel and patients if hazardous drug handling procedures were standardized. A task force was created, a preimplementation survey was distributed, and meetings were held monthly to discuss sections of USP <800> identified as the most challenging to implement. The task force focused on an assessment of risk tool, hot topics, cleanroom design, and a detailed analysis of controversial medications. After the first year of meetings, a postimplementation survey was distributed, and the results were analyzed. The task force created significant value for the participants and achieved the goal of facilitating efficient USP <800> implementation resulting in greater compliance and consistency across the multiple health systems represented. Over 5,100 beds and 200 clinic sites were affected by this task force's efforts. Nearly three-fourths (73%) of respondents reported that the task force was "extremely helpful," and the majority (64%) of respondents adopted most or all (81%-100%) of the task force's assessment of risk choices. Prioritization of tasks, information sharing, and decision-making were areas where the individual leaders were most supported. Creating a structure to eliminate barriers and facilitate collaboration among regional pharmacy leaders provided a framework for successful implementation of USP <800> requirements. This interdependent leadership model produced innovative and standardized solutions and should be considered when addressing complicated initiatives that impact the profession.

Spatial and Temporal Variability in Antineoplastic Drug Surface Contamination in Cancer Care Centers in Alberta and Minnesota.

The health risks of exposure to antineoplastic drugs (ADs) are well established, and healthcare professionals can be exposed while caring for cancer patients receiving AD therapy. Studies conducted worldwide over the past two decades indicate continuing widespread surface contamination by ADs. No occupational exposure limits have been established for ADs, but concerns over exposures have led to the development of guidelines, such as United States Pharmacopeia (USP) General Chapter <800> Hazardous Drugs-Handling in Healthcare. While recommending regular surveillance for surface contamination by ADs these guidelines do not provide guidance on sampling strategies. Better characterization of spatial and temporal variability of multidrug contamination would help to inform such strategies. We conducted surface-wipe monitoring of nine cancer care centers in Alberta, Canada and Minnesota, USA, with each center sampled eight times over a 12-month period. Twenty surfaces from within pharmacy and drug administration areas were sampled, and 11 drugs were analyzed from each wipe sample. Exposure data were highly left-censored which restricted data analysis; we examined prevalence of samples above limit of detection (LOD), and used the 90th percentile of the exposure distribution as a measure of level of contamination. We collected 1984 wipe samples over a total of 75 sampling days resulting in 21 824 observations. Forty-five percent of wipe samples detected at least one drug above the LOD, but only three of the drugs had more than 10% of observations above the LOD: gemcitabine (GEM) (24%), cyclophosphamide (CP) (16%), and paclitaxel (13%). Of 741 wipe samples with at least one drug above LOD, 60% had a single drug above LOD, 19% had two drugs, and 21% had three drugs or more; the maximum number of drugs found above LOD on one wipe was 8. Surfaces in the compounding area of the pharmacy and in the patient area showed the highest prevalence of samples above the LOD, including the compounding work surface, drug fridge handle, clean room cart, passthrough tray, and hazardous drug room temperature storage, the IV pump keypad, patient washroom toilet handle, patient washroom door handle, nurses' storage shelf/tray, and patient side table. Over the course of the study, both 90th percentiles and prevalence above LOD varied without clear temporal patterns, although some centers appeared to show decreasing levels with time. Within centers, the degree of variability was high, with some centers showing changes of two to three orders of magnitude in the 90th percentile of drug concentrations month to month. A clear difference was observed between the six centers located in Alberta and the three in Minnesota, with Minnesota centers having substantially higher percentages of samples above the LOD for CP and GEM. Other factors that were associated with significant variability in exposures were drug compounding volume, size of center, number of patients seen, and age of the center. We hope that demonstrating variability associated with drug, surface, clinic-factors, and time will aid in a better understanding of the nature of AD contamination, and inform improved sampling strategies.

Report on 2020 Safe to Touch Consensus Conference on Hazardous Drug Surface Contamination.

The 2020 Safe to Touch Consensus Conference on Hazardous Drug Surface Contamination was convened in order to gather subject matter experts in the field of hazardous drug (HD) handling to develop consensus statements regarding surface contamination monitoring for adoption by stakeholders in the drug supply chain, policy, and healthcare arenas. The Safe to Touch conference convened virtually on September 22, 24, and 26, 2020. An expert panel of healthcare providers with experience in HD handling, monitoring, and research; pharmacy and nursing operations; and medication safety led the conference. An experienced audience of approximately 25 reaction panel members provided feedback to the panel via a preconference survey, during the conference, and at a postconference virtual town hall. Additionally, expert speakers presented on a range of issues, including the impact of HD surface contamination on health, current regulations and standards, surface contamination monitoring technologies, and variables impacting surface contamination testing. At the end of the conference, the expert panel developed 11 consensus statements and corresponding recommendations that should be widely disseminated in order to educate individuals regarding the impact of HD surface contamination and increase the scope of HD surface contamination monitoring. Institutions involved in the handling of HDs should set short- and long-term goals for implementation of applicable consensus statements.

Evaluation of an Interprofessional Training Program to Improve Cancer Drug Therapy Safety.

Drug therapy for cancer is a high-risk, high-volume clinical intervention that requires interprofessional teams. Given the complexity of anticancer drug therapy and safety concerns, an interdisciplinary team developed a novel training program for oncology registered nurses and pharmacists to improve cancer drug safety. Participants completed preworkshop learning assessments and received access to web-based modules on six topics: hazardous drug handling, drug extravasation, hypersensitivity reaction management, sepsis recognition, immune checkpoint inhibitor toxicities, and oral oncolytic adherence. In a 7-hour workshop, participants applied module content in interactive exercises and high-fidelity simulations. Preworkshop and postworkshop questionnaires assessed changes in knowledge and confidence in each topic. Program satisfaction and changes to clinical practice or policies were assessed 3 months after the workshop. Two hundred ninety-two nurses and 82 pharmacists applied to participate, and 103 (35%) and 44 (54%) have participated, respectively. Long-term follow-up data were available on 133 (90%) participants. Change scores in confidence to meet program objectives increased between pre- and postworkshop (range of increase 0.6-0.8, P < .01). Knowledge scores increased significantly between pre- and postworkshop (average improvement of 3.2 points, P < .01). Overall program satisfaction was high (mean 5.0, standard deviation [0.2] on a five-point scale). Seventy-seven (60%) reported that they had made at least one clinical practice or institutional policy change at 3 months. An interprofessional education program with online modules, in-person interactive sessions, and simulation activities is a promising strategy to deliver cancer drug safety content to practicing oncology clinicians.

Comprehensive tackling to the safe handling of hazardous drugs: a multidisciplinary approach to clinical practice.

The aim of this study is to present the adaptation and implementation of the recommendations of the National Institute for Safety and Health at Work (Instituto Nacional de Seguridad y Salud en el Trabajo - INSHT) in the authors' hospital to achieve a safer handling of hazardous drugs. In 2016, INSHT published the first document on hazardous drugs in Spain. In the authors' center, a project was developed to implement the recommendations presented in that document in 2 phases: 1) analysis: to identify drugs and processes susceptible to not being handled as hazardous, and to search for safer alternatives and preventive measures; and 2) development: to ensure information, training, the adaptation of standardized work procedures, the minimization of risks associated with handling, safety devices, personal protective equipment (PPE), as well as health monitoring. The authors detected 80 commercial presentations manipulated without adhering to safety conditions, mainly oral (74%) from lists 1 (7.5%), 2 (37.5%) and 3 (55%) of the National Institute for Occupational Safety and Health. The following measures were envisaged to reduce the risk: introducing new presentations (4 lower doses, 1 liquid dose) and centralizing new preparations in the pharmacy service (11 oral formulas, 6 parenteral drugs). Management, spillage and exposure procedures were adapted. Safety measures were included in the prescription and administration applications, and there were some indications of risks in the storage. Overall, 48 referents and 690 nurses were trained. Each unit was provided with PPE and safety devices (e.g., closed systems, RX CRUSH®). The steps prior to the administration were moved to the patient's bedside to align patient and professional safety. During the first 6 months after the implementation, 22 cases of pregnancy (64% among the nursing staff), 4 cases of lactation, and 1 case of conceiving problems were reported. In the cases of oxytocin and the repackaging of list 3, risk management was applied. The multidisciplinary approach has allowed to achieve a global and safer control of hazardous drugs with a minimal impact on the center. It is important to continuously evaluate the effects of these measures, and to take into account the data of this analysis and any possible new evidence. Int J Occup Med Environ Health. 2020;33(5):621-34.

Safe handling system construction for hazardous drugs (HDs) through the HD exposure surveillance by National Hospital Organization Network in Japan.

e14147 Background: In Japan, much labor has been devoted to handle occupational exposure to hazardous drugs (HDs) after the publication of a guideline for preventing HD exposure on cancer treatments in 2015. However, the safe HD handling systems have not yet constructed in Japanese hospitals. To find out the current HD exposure and construct the safe HD handling system, a multi-institutional surveillance of HD exposure in the National Hospital Organization (NHO) cancer hospitals was commenced from Feb 2016 to Mar 2018. Methods: Thirty-two NHO institutes joined in this survey. HD surveys were performed 3 times in each institute, evaluating cyclophosphamide and fluorouracil exposures using wipe and sampling sheet methods at 18 places in outpatient chemotherapy and pharmacology units. To share information and discuss about HD exposure handling procedures, the study group meeting was held several times. Furthermore, HD handling system in each hospital was evaluated using handling system scoring established by Yoshida in Osaka Institute of Public Health. As an additional study, factors affecting commitment wills of staffs were also evaluated during the safe HD handling system construction using a multiple regression model. Results: As HD control systems constructed, HD exposure in each hospital was improved gradually with construction of the handling system. Staffs’ commitment to their institutes was shown as the result of safety awareness improvement induced by the HD safe handling system construction (standardization coefficient β: 0.346). Conclusions: HD exposures were improved in NHO cancer hospitals through the HD exposure evaluation with constructions of the safe HD handling system.

Global oncology pharmacy response to COVID-19 pandemic: Medication access and safety.

Response, action, and adaptation of the way health services are delivered will impact our ability to provide optimized and continuity of care while acting within resource constraints imposed by COVID-19. Care for patients with cancer is particularly important given increased infection rates and worse outcomes from COVID-19 in this patient population, as well as potential adverse outcomes if treatment pathways need to be compromised. In this commentary, we provide a global oncology pharmacy perspective (including both developed and developing nations) on how COVID-19 has impacted access to and delivery of cancer therapies. This perspective was prepared by the International Society of Oncology Pharmacy Practitioners, with input from national and regional oncology pharmacy practice groups (42 practice leaders from 28 countries and regions) who contributed to a snapshot survey between 10 and 22 April 2020. Specifically, we highlight challenges related to safe handling of hazardous drugs and maintaining high-quality medication safety standards that have impacted various stakeholders.

Hazardous Drug Residues in the Home Setting: Worker Safety Concerns.

Safety concerns have existed for more than 40 years about how hazardous drug (HD) exposure contributes to adverse health outcomes in health care workers. Careless handling causes toxic HD residues to infiltrate hospital and ambulatory care settings and can even be tracked to patient homes. Little is known about the adverse health outcomes experienced by exposed caregivers. The December 1, 2019, release of new regulations will enforce health care organizations to minimize risk to all health care workers by implementing the US Pharmacopeia (USP) General Chapter<800>Hazardous Drugs-Handling in Healthcare Settings safety standards. Worker safety measures include wearing personal protective equipment, even in home care settings.

Assessment of unintended volume loss of six closed system transfer devices.

Closed system transfer devices (CSTDs) are used to prepare and administer hazardous drugs. Previous studies have explored the vapor and fluid containment performance of CSTDs. A less obvious consideration is the effect of CSTD use on the intended dose for small volume administrations. We assessed six CSTDs to determine if they contribute to volume loss and delivery of less than the intended dose during simulated drug administration. Using an analytical balance, we obtained the mass of each CSTD at four points during simulated drug preparation and subcutaneous administration using sterile water. We used the masses to determine the average volume loss (VL) for each CSTD. Using ANOVA, we identified significant differences in volume loss (VL) among the mean VL (F(6,59) = 18.45, p = 6.19 × 10-12) for the six CSTDs and control (no CSTD). Four CSTDs had a VL that was statistically different than the control (p < 0.05); the VL for two CSTDs was not statistically different than the control (p > 0.05). Volume loss did not depend on administration volume. Volume loss performance varied among CSTDs. Volume loss may be clinically significant for small volumes but is not likely clinically significant for larger volumes. It is the authors' opinion that 3 mL represents a reasonable administration threshold below which volume loss should be considered clinically significant. Users should consider volume loss in context of the tasks, drugs, users, and environments where CSTDs will be used. The United States Pharmacopeia (USP) General Chapter <800>: Hazardous Drugs-Handling in Healthcare Settings recognizes the lack of CSTD performance standards. USP <800> recommends independent performance evaluation of CSTDs based on peer-reviewed studies. Our study adds to the comparative performance evaluations of CSTDs available on the market at the time of this review.

Challenges of Using Closed System Transfer Devices With Biological Drug Products: An Industry Perspective.

Hazardous drug is a common term used by the National Institute of Occupational Health and Safety (NIOSH) to classify medications that may induce adverse mutagenic and reproductive responses in health care personnel. NIOSH publishes a list of drugs it defines as hazardous where it may be appropriate for health care workers to take protective measures to reduce the potential for occupational exposure. Recent updates and proposed updates to this list have included large molecule biological products with oncology indications. Both NIOSH and USP <800> recommend the use of closed system transfer devices (CSTDs) during compounding. CSTDs are required for administration of prepared solution in NIOSH. However, USP has suggested that the principles of <800> are broadly applicable to hazardous drug handling activities across all facility types. USP encourages the widespread adoption and use of <800> across all health care settings, which many health care workers have interpreted beyond compounding to include administration and preparation of conventionally manufactured sterile products per approved labeling. Although the use of CSTDs may reduce exposure of health care personnel to chemotherapy agents in health care setting, the impact of CSTDs on quality of biologic drug products, including monoclonal antibodies and other proteins, is not fully understood. To complicate this issue further, there are several commercially available CSTDs in the market which have different fluid paths and material of construction that comes in contact with the drug. Testing every combination of CSTD and drug product for potential incompatibilities can be a labor intensive and impractical approach and cause delay in getting essential drugs to patients. A panel discussion was held at a recent American Association of Pharmaceutical Scientists 2018 PharmSci 360 conference to discuss the impact of CSTDs on biologics. Impact on subvisible and visible particulates and impact to other product quality attributes such as high molecular weight species formation upon contact with CSTDs were reported in American Association of Pharmaceutical Scientists meeting. Impact to deliverable dose, holdup volumes of various CSTDs, and stopper coring were also reported that has significant impact to patient safety. Given the fact that USP chapter <800> will be implemented in December 2019, feedback from health authorities regarding the use of CSTDs for biological drug products is needed to provide an appropriate risk/benefit balance to ensure patient safety and quality of the biologic drug product while also protecting the health care worker and the environment. The purpose of this commentary is to provide an industry perspective on the challenges during the use of CSTDs for biologic drug products and is intended to raise caution and awareness on the benefits and shortcomings of these devices.