Case Studies: Assessment of CSTDs for Mitigating Contamination of Chemotherapy Agents While Compounding 

The Critical Role of Advanced Technologies in Minimizing Risks from Hazardous Drug Handling

The preparation and administration of hazardous drugs, particularly chemotherapy agents, present significant contamination risks. These processes put both healthcare staff and patients in contact with dangerous chemicals, potentially leading to serious health issues such as dermatological problems (e.g., rashes and hypersensitivity reactions), reproductive disorders, and chronic conditions. The threat of liver damage from prolonged exposure highlights once more the necessity for comprehensive health monitoring and the implementation of protective strategies. 

The National Institute for Occupational Safety and Health NIOSH  emphasises managing these risks to ensure high levels of occupational safety in pharmacies, compounding centres, and other healthcare facilities. Studies published in Springer and the Oncology Nursing Society’s journal have shown the adverse effects of hazardous drugs not only on individuals but also on the workplace environment, advocating for strict contamination control measures. This includes using closed-system transfer devices and automation solutions to mitigate occupational exposure to these environmental contaminants. 

Several case studies illustrate the effectiveness of such modern technologies in improving safety levels in pharmacies and hospitals. These real-life examples highlight the practical advantages and challenges of implementing CSTDs, offering a deeper understanding of their critical role in safeguarding healthcare communities and environments.

Mitigating Hazardous Drug Surface Contamination: Evaluating the Efficacy of Standardized Cleaning and Closed System Transfer Devices 

Healthcare professional using CSTDs for safe compounding of medicines to prevent hazardous drug contamination

A study assessed the reduction of hazardous drug surface contamination in pharmacy compounding and administration areas through standardised cleaning workflows and closed system transfer devices. It aimed to mitigate the risks hazardous drugs pose to healthcare workers and patients by comparing the effectiveness of these interventions. The research focused on evaluating contamination levels post-implementation of enhanced cleaning protocols alongside CSTD utilisation. 

Methodology

Conducted across six different areas within pharmacy and nursing departments, the procedure involved the collection and analysis of 90 individual samples for five commonly compounded hazardous drugs over initial phase, 3-month, and 6-month intervals. The assessment utilised a rigorous testing protocol to measure the presence of hazardous drug residues on surfaces. 

Results

The findings demonstrate that through standardised cleaning protocols and the integration of CSTDs, healthcare facilities can significantly reduce the risk of exposure to hazardous drugs. This comprehensive evaluation across multiple time points and locations revealed no detectable residue in all 90 samples analysed, highlighting the critical role of meticulous cleaning processes and the employment of secondary engineering controls like CSTDs in maintaining a safer work environment. 

Conclusions

The study supports the adoption of standardised cleaning protocols and closed system transfer devices as effective strategies for maintaining low levels of surface contamination. By demonstrating the effectiveness of these strategies, the study offers valuable insights for healthcare facilities aiming to enhance occupational safety and patient care standards.   

Assessing the Performance of Closed System Drug-Transfer Devices in Vapor Containment 

Evaluating CSTDs in a lab for vapour containment to ensure healthcare safety during drug transfer.

An independent study evaluated the vapour containment performance of six commercially available closed-system drug transfer devices against the draft vapour protocol released by NIOSH. This research aimed to quantitatively assess the effectiveness of these CSTDs in containing gas/vapour within a controlled test environment. Utilizing 70% isopropyl alcohol (IPA) as a challenge agent, the study simulated drug compounding and administration processes, measuring IPA vapour concentrations that escaped the devices.

Methodology

The methodology closely adhered to the NIOSH draft protocol, incorporating two specific tasks outlined by NIOSH, with additional steps included to thoroughly evaluate the devices. Each device underwent these tasks ten times to ensure a comprehensive assessment.  

Results 

The results revealed a significant variance in performance among the tested closed system transfer devices: only three devices managed to maintain IPA vapour release below the 1.0 ppm threshold defined by NIOSH for successful containment across all tasks. Notably, the Equashield device demonstrated superior performance, consistently maintaining vapour release levels well below the 1.0 ppm threshold, affirming its efficacy as a truly closed system under the robust vapour challenge posed by the study. 

Conclusions

This study contributes to the safety and efficacy discourse of CSTDs in healthcare settings, suggesting that future testing and protocol adjustments consider these devices’ operational realities. By demonstrating that only half of the evaluated closed-system drug transfer devices met NIOSH’s quantifiable performance threshold, the research highlights the need for healthcare facilities to critically assess CSTD technology choices. The standout performance of the Equashield device underscores its effectiveness in protecting healthcare workers from hazardous drug exposure, making it a noteworthy option for facilities prioritising safety and efficiency in drug handling processes.

Evaluating Vapor Containment Efficacy of CSTDs 

Another study evaluated the vapour containment capabilities of CSTDs utilizing various containment technologies. Conducted in partnership with the Health and Safety Laboratory (HSL) in Buxton, UK, the research aimed at reviewing the draft protocol proposed by NIOSH for CSTD evaluation. The study compared the effectiveness of devices employing physical barriers against those using air-cleaning technology in containing hazardous drug vapours. 

Methodology

The methodology replicated the NIOSH test protocol within a specially constructed environmental test chamber, incorporating both the original protocol instructions and the device manufacturers’ instructions for use (IFU). The evaluation involved simulated pharmacy manipulations, including drug reconstitution and IV bag preparation, using a surrogate mixture to challenge the systems. Vapour release was measured using advanced detection technologies, providing a comprehensive analysis of each system’s containment performance.  

Results 

The study highlighted differences in vapour containment among the tested devices, indicating that adherence to manufacturer-specific IFUs is crucial for maintaining the integrity of CSTD operation and ensuring an accurate assessment of vapour containment efficacy. 

Conclusions

This study contributes valuable insights into the safety protocols necessary for handling hazardous drugs in healthcare settings, aiming to enhance worker protection against potential drug vapour exposure.

Assessing Syringe Plunger Contamination in Hazardous Drug Handling: A Comparative Analysis of Closed System Transfer Devices 

In a comparative analysis, researchers examined cyclophosphamide contamination on syringe plungers using different CSTDs in oncological compounding. The study compared the performance of Becton Dickinson’s syringe plungers with Phaseal™ CSTDs against those from Equashield™, assessing their ability to minimize hazardous drug exposure during chemotherapy preparation and administration.

 Methodology

Utilizing the ChemoGlo™ sampling kit for precise analysis, the study tested cyclophosphamide contamination levels on syringe plungers after conducting multiple drug transfer cycles within a Forma Class II, 2A Biological Safety Cabinet. The syringes were categorised into three groups, each subjected to a set number of drug transfer cycles to simulate varying degrees of usage intensity. 

Results

The findings revealed significant contamination levels exceeding 2000 ng when used with Phaseal™ CSTDs, highlighting a potential risk of hazardous drug exposure. Conversely, Equashield™ syringes demonstrated no detectable contamination, underscoring their superior capability in preventing drug leakage and ensuring a safer oncology compounding environment. 

Conclusions

This comparative study underscores the critical importance of employing effective CSTDs to safeguard healthcare workers from exposure to hazardous drugs during chemotherapy preparation and administration. The superior performance of Equashield™ syringes in maintaining a contamination-free compounding process emphasises the need for adopting advanced CSTDs in oncology practices. 

Assessing the Impact of Closed System Drug Transfer Devices on Antineoplastic Drug Safety in Healthcare Settings

A comprehensive study critically examined the effectiveness of CSTDs, specifically TexiumTM/SmartSiteTM and Equashield® II, in minimizing leakage and contamination during the compounding of antineoplastic drugs in a centralized cytotoxic drug preparation unit. The primary aim of this research was to assess the capability of these leading CSTDs to reduce occupational exposure to hazardous drugs, with a particular focus on gemcitabine (GEM), by preventing leaks and spills during the drug preparation and administration process.  

Methodology

The research involved a detailed analysis of wipe and pad samples collected from inside and outside the drug preparation area over five years. The focus was on detecting GEM contamination to evaluate the sealing efficiency of the CSTDs used.   

Results 

Findings indicated a significant reduction in GEM contamination with the adoption of Equashield® II, demonstrating its superior ability to prevent drug leakage and ensure a safer working environment. 

Conclusions  

This investigation highlights the critical role of CSTDs in safeguarding healthcare workers from exposure to hazardous antineoplastic drugs. The Equashield® II system, in particular, was shown to be highly effective in eliminating risks of spills and leaks. 

Evaluating Efficiency, Ease of Use, and Cost of Closed System Transfer Devices for Chemotherapy Administration in Veterinary Oncology 

This study assessed the treatment time, ease of use, and associated costs of administering chemotherapy using CSTDs versus traditional methods in a veterinary setting. The primary goal was to evaluate the operational efficiency, user experience, and financial considerations of two prominent CSTDs, Equashield™ and PhaSeal®, compared to conventional chemotherapy administration methods. 

Methodology

The study employed a prospective experimental simulation approach, engaging veterinary technicians from oncology speciality practices. 

Results

The investigation revealed that Equashield™ facilitated the fastest administration times and was also found to be easier to use than PhaSeal® and the no-CSTD approach. 

Conclusions

This research underscores the importance of integrating CSTDs into veterinary oncology to safeguard healthcare workers without detracting from treatment efficacy. 

Improving Safety in Hazardous Drug Handling: Recommendations for Healthcare Facilities and Compounding Centres

Healthcare facilities implementing safety measures for hazardous drug handling

  • Adopting closed system transfer devices (CSTDs) is recommended to reduce contamination risks. CSTDs have proven effective in maintaining a safer working environment by significantly lowering the risk of exposure to hazardous drugs. 
  • Facilities are encouraged to evaluate and select CSTDs based on their proven performance in vapour containment and their ability to prevent drug leakage and syringe plunger contamination.  
  • Furthermore, the implementation of standardised cleaning protocols alongside the use of CSTDs is crucial. Rigorous, consistent cleaning methods have been shown to effectively eliminate hazardous drug residues on surfaces, further safeguarding healthcare personnel and patients.  
  • Healthcare facilities should adopt a comprehensive approach that includes both technological solutions like CSTDs and enhanced cleaning workflows to ensure the highest levels of safety. 
  • Training and education on the correct use of CSTDs and adherence to cleaning protocols are essential for healthcare workers. Regular competency assessments and ongoing education on handling hazardous drugs should be instituted. 
  • Evaluating the efficacy of CSTDs and cleaning protocols should be an ongoing process. Healthcare facilities are advised to conduct periodic reviews and assessments of their hazardous drug handling practices. 
  • Finally, the financial aspect of adopting CSTDs should be considered, with an emphasis on cost-effectiveness without compromising safety. The studies suggest that while initial investments may be required, the long-term benefits justify the expenditure. Healthcare facilities should explore various CSTD options, considering both upfront costs and long-term savings in terms of improved occupational safety and health outcomes.

By adhering to these recommendations, healthcare facilities and compounding centres can significantly enhance the safety of their environments, protecting both their workers and patients from the risks associated with handling hazardous drugs.

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The Impact of Standards on Compounding Pharmacies and Outsourced Facilities 

The meticulous compounding of hazardous medicines is a critical aspect of healthcare, demanding the highest quality standards to ensure patient safety and treatment efficacy. This article aims to present how these standards are upheld within the British healthcare system. 

The Regulatory Framework for Compounding Hazardous Medicines in the UK  

In the UK, a carefully structured regulatory framework governs the compounding and administration of hazardous medicines. Here’s a detailed breakdown of the key organizations involved and how they interact with each other. 

Medicines and Healthcare Products Regulatory Agency (MHRA)

Primary Role: The MHRA stands at the forefront, overseeing all aspects of medicine and medical device regulations across the UK. 

Interactions: It sets the overarching standards and guidelines, directly influencing the operations and practices of other regulatory bodies like the GPhC, PASG, and BOPA.

The main responsibilities of the MHRA for compounding hazardous medicines include:  

  • Setting Standards and Guidelines: Developing and enforcing guidelines for the safe compounding of hazardous drugs, ensuring adherence to Good Manufacturing Practice (GMP) standards. 
  • Quality Assurance: Overseeing the quality management systems in pharmacies and hospital settings to ensure that compounded medicines meet the required safety and quality standards. 
  • Monitoring and Inspection: Conducting regular inspections of compounding facilities to ensure compliance with regulatory requirements and GMP. 
  • Pharmacovigilance: Implementing robust pharmacovigilance systems to monitor adverse drug reactions and ensure timely reporting and action on any safety concerns associated with compounded medicines. 
  • Enforcement and Compliance: Taking appropriate enforcement actions against non-compliance and ensuring that pharmacies and hospitals adhere to the established compounding standards and regulations. 

General Pharmaceutical Council (GPhC) 

Primary Role: This council regulates pharmacy professionals and pharmacies, ensuring compounding processes meet the highest safety and quality standards. 

Interactions: Working in line with MHRA’s regulations, the GPhC is responsible for implementing these standards at the pharmacy level, collaborating closely with the PASG to ensure compliance and enforcement.

The main responsibilities of the GPhC in regulating the compounding of hazardous medicines include:

  • Setting and Enforcing Standards: Establishing clear, rigorous standards for the compounding of hazardous drugs in pharmacies and hospitals. 
  • Inspection and Monitoring: Regularly inspecting pharmacy facilities to ensure compliance with compounding standards and safe practices. 
  • Guidance and Training: Providing guidance and resources for pharmacy professionals regarding the safe compounding of hazardous drugs, including training requirements. 
  • Quality Assurance: Ensuring that pharmacies have robust quality assurance processes in place for the compounding of hazardous drugs. 
  • Pharmacy Registration and Compliance: Overseeing the registration of pharmacies and ensuring they comply with the legal and professional requirements for compounding hazardous drugs. 
  • Risk Management: Implementing and enforcing risk management strategies to minimise the risks associated with the compounding of hazardous drugs.

British Pharmacopoeia Commission (BPC)

Primary Role: The BPC sets the quality standards for medicinal substances, fundamental for compounding processes. 

Interactions: It provides the scientific basis for MHRA’s regulations, guiding the Expert Advisory Groups in advising on best practices for medicinal products. 

Key responsibilities of the British Pharmacopoeia Commission (BPC) include:

  • Standard Setting for Medicinal Substances: Developing and maintaining the British Pharmacopoeia, which provides the official standards for the quality of medicinal substances, including those used in compounding hazardous drugs. 
  • Guidance on Formulations: Offering detailed guidance on the formulation of medicines, ensuring that compounded drugs meet the necessary quality and safety standards. 
  • Ensuring Consistency and Quality: Ensuring the consistency and quality of medicinal substances and preparations, which is critical in the compounding process, especially for hazardous drugs. 
  • Updating Standards: Regularly updating and revising the standards in the British Pharmacopoeia to reflect advancements in pharmaceutical science and technology. 
  • International Collaboration: Collaborating with international bodies to align the UK’s pharmaceutical standards with global best practices

BPC works in conjunction with the MHRA to align the standards with broader public health protections and medicine regulations. 

For the latest information on the standards and guidelines set by the BPC, healthcare professionals and institutions like yours can refer to the British Pharmacopoeia, which is now legally effective. Check the 2024 edition here.  

The Commission on Human Medicines 

Primary Role: The Commission on Human Medicines is pivotal as an advisory body, providing critical guidance and recommendations to ensure the safe and effective use of medicinal products in the UK. 

Interactions: It plays a significant role in advising the Licensing Authority, impacting the regulation of medicines by the MHRA. The Commission’s evaluations and recommendations directly inform the regulatory landscape for compounding hazardous drugs, influencing policy and practice at all levels. 

Key responsibilities of the Commission on Human Medicines in this context include: 

  • Advisory Role: Providing expert advice to the Licensing Authority on the safety, quality, and efficacy of medicinal products, including those used in compounding hazardous drugs. 
  • Evaluation of Safety and Efficacy: Assessing the safety and efficacy of medicinal products, particularly those classified as hazardous, to ensure they meet the required standards for patient use. 
  • Risk-Benefit Analysis: Conducting risk-benefit analyses of medicinal products to guide decision-making processes regarding their use and compounding. 
  • Guidance on Medicinal Standards: Offering guidance on standards and best practices for the compounding and use of hazardous drugs, based on the latest scientific and clinical evidence. 
  • Monitoring Adverse Drug Reactions: Monitoring adverse drug reactions and other safety concerns related to compounded hazardous drugs and advising on appropriate actions to mitigate risks. 
  • Policy Recommendations: Making policy recommendations to regulatory bodies to enhance the regulatory framework governing the compounding of hazardous drugs. 

Expert Advisory Groups (EAG) 

Primary Role: These groups offer specialized advice on various aspects of medicinal products. 

Interactions: They play an advisory role to both the MHRA and BPC, impacting the development and refinement of guidelines for hazardous drug compounding. 

Appointed by the Commission on Human Medicines and the British Pharmacopoeia Commission the Expert Advisory Groups play a crucial consultative role in the regulation of compounding hazardous drugs in hospitals and pharmacies in the UK. They consist of experts in various fields of medicine and pharmaceuticals.

The main responsibilities of these Expert Advisory Groups include:

  • Providing Specialized Advice: Offering expert guidance on specific issues related to the compounding of hazardous drugs, including safety, quality, and efficacy. 
  • Recommendations on Standards and Practices: Recommending standards and best practices for the compounding of hazardous drugs, ensuring they align with current scientific understanding and clinical evidence. 
  • Reviewing and Updating Guidelines: Assisting in the review and updating of guidelines and standards, particularly those published in the British Pharmacopoeia and other regulatory documents. 
  • Risk Assessment and Management: Contributing to the assessment and management of risks associated with the handling and compounding of hazardous drugs. 
  • Innovation and Research Support: Providing insights into the latest research and technological advancements that can impact the compounding of hazardous drugs and suggesting ways to incorporate these into current practices. 
  • Liaison and Coordination: Facilitating communication and coordination between the Commission on Human Medicines, the British Pharmacopoeia Commission, and other regulatory bodies to ensure cohesive and comprehensive regulation

The Licensing Authority 

  • Primary Role: The Licensing Authority, comprising the Secretary of State and the Minister for Health, Social Services, and Public Safety, is entrusted with the critical task of ensuring that the compounding of hazardous drugs in the UK adheres to stringent safety and quality standards. 
  • Interactions: It is the body responsible for the issuance and regulation of licenses for the manufacturing, assembling, or importing of medicinal products. By ensuring compliance, enforcing regulations, and updating policies, the Licensing Authority shapes the environment within which pharmacies and manufacturers operate, thus safeguarding public health. 

Key responsibilities of the Licensing Authority include: 

  • Granting and Regulating Licenses: Issuing licenses for the manufacturing, assembling, or importing of medicinal products, including hazardous drugs. 
  • Quality and Compliance Oversight: Ensuring that licensed entities adhere to the required quality standards for compounding hazardous drugs. 
  • Regulation Enforcement: Enforcing regulations related to the compounding of hazardous drugs, including imposing penalties for non-compliance. 
  • Policy Formulation: Developing and updating policies and guidelines to ensure the safe handling and compounding of hazardous drugs. 
  • Monitoring and Auditing: Conducting inspections and audits of facilities to ensure compliance with established standards and regulations. 
  • Risk Management: Implementing risk management strategies to minimise potential hazards associated with the handling and compounding of hazardous drugs. 

Pharmaceutical Aseptic Services Group (PASG)

Primary Role: The PASG focuses on aseptic preparation, upholding stringent standards for the compounding of hazardous drugs. 

Interactions: It aligns its practices with the guidelines set by MHRA and GPhC, conducting audits and overseeing quality control in pharmacy environments. 

This group operates under the framework of the Royal Pharmaceutical Society, focusing on establishing and maintaining high standards for aseptic preparation and ensuring the safety and efficacy of compounded drugs. 

Key responsibilities of the Pharmaceutical Aseptic Services Group in regulating the compounding of hazardous medicines include:

  • Standard Setting: Developing and maintaining standards for aseptic compounding of hazardous drugs, ensuring practices meet national and international guidelines. 
  • Quality Assurance and Control: Implementing quality assurance and control measures to guarantee the sterility and safety of compounded drugs. 
  • Risk Management: Establishing robust risk management protocols to minimise the risks associated with handling and compounding hazardous drugs. 
  • Training and Education: Providing specialized training and educational resources to healthcare professionals involved in aseptic compounding. 
  • Policy Development: Formulating policies and guidelines for the safe compounding of hazardous drugs, including the use of Personal Protective Equipment (PPE) and containment strategies. 
  • Monitoring and Compliance: Conducting regular audits and inspections to ensure compliance with established standards and procedures in aseptic compounding. 

Royal Pharmaceutical Society (RPS)

Primary Role: The RPS establishes national standards for aseptic preparation services in the UK, ensuring the quality and safety of compounded hazardous medicines. 

Interactions: Collaborates with the NHS Pharmaceutical Quality Assurance Committee to audit and assure the quality of pharmacy aseptic units, aligning with MHRA guidelines and supporting the framework established by the GPhC and PASG. 

The RPS is instrumental in developing and maintaining national standards for the aseptic preparation of medicines, with a particular focus on ensuring the quality and safety of hazardous drug preparations. In close partnership with the NHS Pharmaceutical Quality Assurance Committee, the RPS has instituted quality standards and auditing processes to uphold the integrity of pharmacy aseptic units. While these standards are tailored to the NHS, they also provide a benchmark for educational purposes and international healthcare entities.

 The main responsibilities of the RPS in regulating the compounding of hazardous drugs include: 

  • Developing national standards that guide aseptic preparation services. 
  • Overseeing the preparation of critical medicines, particularly in settings that involve unlicensed hospital aseptic preparation units. 
  • Collaborating to establish audit programs that maintain the high quality of aseptic units within the NHS. 
  • Advising on the practical application of these standards through resources such as the “Quality Assurance of Aseptic Preparation Services: Standards Handbook.” 

British Oncology Pharmacy Association (BOPA) 

Primary Role: BOPA specifically addresses oncology pharmacy practices, emphasizing the safe compounding and administration of hazardous drugs in this field. 

Interactions: Operating under MHRA’s regulatory framework, BOPA collaborates with both the NHS and UKONS to develop specialized training and policies for oncology-related scenarios. 

BOPA plays a significant role in guiding and influencing the practice of compounding hazardous drugs, particularly in the field of oncology, within hospitals and pharmacies in the UK. BOPA’s focus is on enhancing patient care and safety in cancer treatments, where handling and compounding hazardous drugs, like chemotherapy agents, require stringent protocols. 

The main responsibilities of BOPA in this context include: 

  • Setting Clinical Standards: Developing and advocating for clinical practice standards in oncology pharmacy, particularly regarding the safe compounding and administration of hazardous drugs. 
  • Providing Education and Training: Offering educational resources and training programs to oncology pharmacy professionals for safe and effective compounding practices. 
  • Promoting Research and Best Practices: Encouraging research in oncology pharmacy and disseminating best practice guidelines for compounding hazardous drugs. 
  • Quality Assurance and Safety: Focusing on quality assurance measures to ensure the safety and efficacy of compounded oncology medications. 
  • Policy and Guidance Development: Contributing to the development of policies and guidance related to oncology pharmacy, including the handling and compounding of hazardous drugs. 
  • Collaboration with Regulatory Bodies: Working alongside healthcare regulatory bodies to influence policy decisions and regulations governing the compounding of hazardous drugs in oncology. 

National Health Service (NHS) 

Primary Role: The NHS oversees broader healthcare practices in the UK, including the safe compounding of hazardous drugs within NHS facilities. 

Interactions: It implements safety protocols and training by MHRA guidelines and coordinates with entities like UHB to enforce local policies and procedures. 

NHS in the UK plays a critical role in regulating the compounding of hazardous drugs in hospitals and pharmacies. This involves overseeing practices to ensure the safety and efficacy of drug preparation, particularly when dealing with cytotoxic and other chemotherapeutic agents that pose significant risks to both healthcare providers and patients.

The main responsibilities of the NHS in this context include: 

  • Establishing Safety Protocols: Implementing comprehensive safety protocols for the handling, compounding, and administration of hazardous drugs. 
  • Staff Training and Education: Providing extensive training and education to healthcare staff, emphasizing the safe handling of hazardous drugs and the use of Personal Protective Equipment (PPE). 
  • Quality Assurance: Ensuring quality assurance in the compounding process, including adherence to aseptic techniques and proper storage conditions. 
  • Risk Assessment and Management: Conducting risk assessments to identify potential hazards and implementing strategies to mitigate these risks. 
  • Regulatory Compliance: Enforcing compliance with relevant laws and regulations, including COSHH (Control of Substances Hazardous to Health) regulations, and ensuring adherence to NHS policies and guidelines. 
  • Monitoring and Auditing: Regularly monitoring and auditing pharmacy aseptic services and compounding units to ensure compliance with safety standards. 

United Kingdom Oncology Nursing Society (UKONS) 

Primary Role: UKONS concentrates on standardizing practices among oncology nurses, particularly in administering Systemic Anti-Cancer Therapy (SACT). 

Interactions: It ensures that nursing practices align with the standards set by BOPA and the training requirements of the NHS, enhancing the safe administration of oncology treatments. 

UKONS plays a pivotal role in regulating the process of compounding hazardous drugs, particularly Systemic Anti-Cancer Therapy (SACT), in hospitals and pharmacies across the UK. The SACT Competency Passport, developed by UKONS, serves as a key tool in this regulation.

The main responsibilities of UKONS in the context of compounding hazardous drugs include:  

  • Standardizing Competencies: Developing and updating the SACT Competency Passport to ensure a standardized level of knowledge and skill among healthcare professionals handling and administering SACT. 
  • Promoting Safe Handling of SACT: Emphasizing the safe handling and administration of SACT to minimize occupational exposure risks to healthcare professionals. 
  • Education and Training: Providing theoretical and practical guidance for the education and training of nurses and other healthcare professionals in the safe administration of SACT. 
  • Clinical Practice Assessment: Implementing a structured approach for clinical practice assessment to ensure practical proficiency in SACT administration. 
  • Annual Reaccreditation: Instituting a process of annual reaccreditation to maintain and update competencies in SACT administration. 
  • Patient-Centred Care Focus: Highlighting the importance of patient-centred care during SACT administration, including patient education and support. 
  • Adaptability to Various Settings: Ensuring that the competencies and guidelines are adaptable to different healthcare settings and roles involved in SACT administration. 
  • Feedback and Continuous Improvement: Encouraging feedback and ongoing improvement of the SACT Competency Passport to align with evolving practices and patient needs in oncology care. 

University Hospitals, Pharmacies and Compounding Centres 

Primary Role: They represent the practical application of these standards in a healthcare facility setting, focusing on safety procedures and staff training. 

Interactions: It adopts and implements policies and procedures in line with NHS and MHRA guidelines, ensuring local compliance and effective risk management.

University Hospitals, pharmacies and compounding centres focus predominantly on establishing rigorous protocols and procedures to manage the risks associated with handling and administering cytotoxic and chemotherapeutic agents. 

Their main responsibilities in this context include: 

  • Developing Safe Handling Procedures: Establishing detailed procedures for the safe prescribing, handling, and administration of cytotoxic and other chemotherapeutic agents. 
  • Staff Training and Competency: Ensuring that medical, nursing, and pharmacy staff are adequately trained and deemed competent in handling hazardous drugs, including specific training for chemotherapeutic agents. 
  • Patient Safety and Consent: Implementing procedures to ensure patient safety, including informed consent processes for patients undergoing treatment with hazardous drugs. 
  • Risk Assessment and Management: Performing thorough risk assessments and management strategies for the use of hazardous drugs in various clinical settings. 
  • Quality Control and Assurance: Overseeing the quality control processes for compounding hazardous drugs, ensuring compliance with aseptic techniques, and correct storage and handling. 
  • Policy Development and Compliance: Developing and maintaining policies in line with national guidelines and regulatory requirements for the safe handling of cytotoxic drugs. 
  • Monitoring and Reporting: Regularly monitoring the handling and administration of hazardous drugs and ensuring the reporting and management of any related incidents or near misses. 

This integrated network, led by the MHRA, and supported by organizations like the GPhC, PASG, BOPA, NHS, and all the others mentioned above ensures that the compounding and administration of hazardous drugs in the UK are not only safe and effective but also centred around the needs of patients. 

How to Apply Good Manufacturing Practice (GMP) Standards When Compounding Hazardous Medicines

Understanding Good Manufacturing Practice in Compounding Hazardous Medicines 

In the intricate world of pharmaceutical compounding, Good Manufacturing Practice (GMP) stands as a beacon of quality and safety. Particularly in the compounding of hazardous medicines, GMP is not just a set of guidelines but a vital framework ensuring that every medication is produced with the highest standards of safety and efficacy. This introduction sets the stage for understanding how GMP standards are meticulously applied in the compounding of hazardous drugs. 

The Role of GMP in Ensuring Consistency, Quality, and Safety for Healthcare Workers Compounding Hazardous Drugs 

By following the GMP standards, pharmacies and healthcare facilities can: 

  • Minimize contamination risks. 
  • Ensure accurate dosing and ingredient mixing. 
  • Maintain an environment that protects both the product and the healthcare professionals involved in compounding. 
  • Uphold stringent quality control throughout the compounding process.

Specific GMP Requirements for UK Compounding Pharmacies and Outsourced Facilities 

Compounding pharmacies in the UK, along with outsourced facilities dealing with hazardous drugs, must adhere to specific GMP requirements. Key steps include:

  • Comprehensive Risk Assessment: Identify potential hazards in compounding processes and implement appropriate safety measures. 
  • Qualified Personnel: Ensure that staff are adequately trained in handling hazardous materials and understand GMP principles. 
  • Facility Design and Maintenance: Design facilities to prevent cross-contamination. Regular maintenance and cleanliness are paramount. 
  • Equipment Validation: Validate all equipment used in compounding to ensure accuracy and safety. 
  • Detailed Documentation: Maintain thorough records of compounding processes, ingredient sourcing, and staff training. 
  • Regular Auditing and Inspection: Periodic audits and inspections are essential to ensure ongoing compliance with GMP standards. 
  • Quality Control Measures: Implement rigorous testing procedures for both raw materials and finished products. 
  • Reporting and Addressing Non-Compliance: Establish protocols for reporting GMP violations and taking corrective actions. 

For a more comprehensive understanding of GMP and its application in compounding hazardous medicines, further resources and training are recommended. 

Best Practices in Quality Control and Assurance for Compounding Hazardous Drugs 

Next, we shift our focus to the twin pillars of quality control (QC) and quality assurance (QA) in the compounding of hazardous drugs. This part of the article emphasizes the critical role these practices play in ensuring that compounded medications not only meet safety standards and comply with GMP but also retain their intended efficacy, especially in high-risk scenarios like aseptic preparations. 

Best Practices in Quality Control and Assurance for Compounding Hazardous Drugs

The Crucial Role of Quality Control and Assurance 

Quality control and assurance in compounding hazardous medicines are paramount due to the high risks involved. As per NHS England’s guidelines, stringent QC and QA practices ensure that compounded medications meet the necessary safety, quality, and efficacy standards (NHS England). This is especially vital in aseptic preparations where the risk of contamination can have dire consequences. 

Quality Control Procedures: A Closer Look

Testing 

Regular and thorough testing is a cornerstone in compounding hazardous drugs. This includes sterility tests, endotoxin tests, and potency checks, as emphasized by the Specialist Pharmacy Service (SPS). 


Documentation and Record-Keeping 

Meticulous documentation is key. This encompasses compounding procedures, outcomes, and any deviations or incidents. 

The NHS England guidance underlines the importance of digital platforms like iQAAPS for effective documentation and compliance management.

Equipment and Processes Validation

Equipment and processes require regular validation to ensure consistent quality. This includes clean rooms, sterilization processes, and compounding techniques. 

Validation ensures that every aspect of the compounding process adheres to predefined standards and is capable of consistently delivering quality products. 

Operator Training and Validation

Compounding personnel must be adequately trained and periodically revalidated to maintain proficiency in handling hazardous drugs. 

As per NHS England’s guidance, this includes assessing and ensuring staff competence in aseptic techniques and handling hazardous substances (NHS England).

Adherence to Standards and Guidelines 

Following established standards, such as those outlined in the “Quality Assurance of Aseptic Preparation Services” by the Royal Pharmaceutical Society and the NHS Pharmaceutical Quality Assurance Committee, is crucial (RPS). 

These standards provide a comprehensive framework covering all aspects of aseptic preparation, including risk management, equipment validation, and staff training. 

Risk Management and Compliance in Compounding Hazardous Medicines

Understanding the Risks in Pharmaceutical Compounding 

The compounding of hazardous drugs in pharmaceutical manufacturing presents a unique set of challenges, demanding meticulous risk management and unwavering compliance with regulatory standards. These processes are critical for ensuring the safety and effectiveness of medications, while also safeguarding the health of those involved in their preparation.

The Critical Role of Risk Assessment 

Risk assessment is the cornerstone of managing potential hazards in pharmaceutical manufacturing, particularly in the compounding of hazardous drugs. It involves a systematic evaluation of processes to identify potential risks to both product quality and personnel safety. 

Identifying Hazards

This initial step involves recognizing all possible risks associated with the compounding of hazardous drugs, ranging from chemical toxicity to environmental contamination. 

The identification of hazards in pharmaceutical compounding requires a multi-faceted approach: 

Comprehensive Inventory: Begin by creating a comprehensive inventory of all substances used in the compounding process. This includes active pharmaceutical ingredients, excipients, and any cleaning agents. Reference the Control of Substances Hazardous to Health (COSHH) Inventory Document for guidance on documenting substances. 

Material Safety Data Sheets (MSDS): Obtain and review the MSDS for each substance, which provides crucial information on chemical properties, toxicity, handling, storage, and disposal requirements. 

Workplace Exposure Limits (WELs): Consult the latest WELs, which are legal limits on the amounts of hazardous substances in the air, as provided by the HSE guidelines, to assess airborne risks. 

Process Analysis: Analyse the compounding process step by step to identify where and how workers might be exposed to hazardous substances. This includes examining handling procedures, the potential for aerosol generation, and points of environmental release. 

Consultation with Experts: Engage with health and safety committees, pharmacists, and industrial hygienists to review procedures and identify potential hazards that may not be immediately obvious. 

Equipment Review: Ensure that all equipment used in the compounding process is examined for containment efficacy. Closed-system drug-transfer devices (CSTDs) should be considered to minimize exposure. 

Legislative Framework: Familiarize yourself with the legislative framework relevant to hazardous drug compounding, such as the COSHH regulations and any specific guidance for pharmaceuticals, to understand the legal requirements for hazard identification. 

Cytotoxic Specificity: For cytotoxic drugs, refer to specialized guidance like the HSE’s “Safe handling of cytotoxic drugs in the workplace” to understand specific risks associated with these potent compounds. 

Evaluating Risks 

Identifying Hazardous drugs with compounding

Once potential hazards are identified, the next critical phase is risk evaluation. This process quantifies the likelihood and severity of the identified risks and their potential impact on both product quality and personnel safety. Here’s how to approach this: 

Use of Risk Matrices: Employ risk matrices to gauge the severity of the hazard and the likelihood of its occurrence. This method combines qualitative and quantitative assessments to prioritize risks. 

Consult WELs and Occupational Exposure Limits: Refer to Workplace Exposure Limits and Occupational Exposure Limits for hazardous substances as outlined by HSE guidelines, to determine acceptable levels of exposure and assess the extent to which current practices exceed these benchmarks. 

Quantitative Exposure Assessments: Perform quantitative exposure assessments for tasks that involve handling hazardous drugs. This includes air monitoring for volatile substances and surface contamination assessments for non-volatile compounds. 

Health Surveillance Data: Review health surveillance data, if available, to understand the historical impact of substance exposure on employees’ health. This data can highlight trends and help assess the potential chronic health risks. 

Severity of Consequences: Assess the severity of potential adverse events on both health and the environment. For instance, consider the implications of exposure to reproductive toxins or the impact of a chemical spill. 

Exposure Duration and Frequency: Evaluate the duration and frequency of exposure to hazardous substances. This includes considering both routine operations and the potential for accidental exposures. 

Mitigation Efficacy: Examine the current control measures in place for their effectiveness. Review incident reports and near-misses to evaluate if current mitigation strategies are sufficient. 

Consultation with Regulatory Bodies: For complex risk evaluations, consider consulting with regulatory bodies or external experts. They can provide insights into risk assessment methodologies that are compliant with current regulations. 

Task-Specific Risks: Use task-based risk assessments for activities involving hazardous drugs, as recommended by the Royal Pharmaceutical Society. This approach looks at the risks associated with the compounding process itself. 

Documentation and Review: Document all findings thoroughly. This documentation should be readily accessible for review and use in future risk assessments and audits. 

By taking these practical steps, organizations can systematically evaluate the risks associated with the compounding of hazardous medicines. This evaluation not only informs the implementation of appropriate safety measures but also ensures that risk mitigation strategies align with the latest health and safety standards, thereby safeguarding both product integrity and occupational health. 

Implementing Mitigation Strategies 

Based on the risk evaluation, appropriate mitigation strategies are developed. These may include engineering controls, like closed-system drug-transfer devices, administrative controls, and the use of personal protective equipment (PPE). 

Continuous Monitoring and Review

Risk assessment is an ongoing process. Regular monitoring and review are crucial for ensuring the effectiveness of the mitigation strategies and for adapting to any changes in processes or regulations.

The Imperative of Regulatory Compliance 

Compliance with regulatory guidelines is not just a legal obligation but a moral imperative in pharmaceutical manufacturing. The guidelines provided by agencies like the Health and Safety Executive (HSE) and the Royal Pharmaceutical Society are designed to prevent adverse events, ensuring the highest standards of safety and efficacy in drug compounding.

Sterile vs. Non-Sterile Compounding Practices 

Sterile vs. Non-Sterile Compounds: Understanding the Basics

Sterile Compounds are medications prepared under strict aseptic conditions to ensure they are free from all forms of microbial life. These compounds are typically used in injections, eye preparations, and other routes of administration where sterility is paramount for patient safety. 

Non-sterile compounds, in contrast, are prepared in a less stringent environment. They include oral medications, ointments, and creams where absolute sterility isn’t a necessity, though quality and safety remain crucial.

Regulations and Best Practices for Sterile Compounding

Aseptic Techniques and Cleanroom Standards 

When it comes to sterile compounding, aseptic techniques are the cornerstone. As outlined in the “Guidance for ‘specials’ manufacturers” by the UK Government, these techniques involve meticulous practices to avoid contamination, including proper hand hygiene and the use of sterilized equipment (GOV.UK). 

The environment where sterile compounding occurs is equally vital. Cleanrooms or controlled environments, adhering to standards such as ISO Class 5, are essential. These spaces are designed to maintain low levels of environmental pollutants and are equipped with High-Efficiency Particulate Air (HEPA) filters to ensure air purity, as emphasized in the “Transforming NHS Pharmacy Aseptic Services in England” report (NHS England). 

Closed System Transfer Devices (CSTDs) 

The use of CSTDs is a critical aspect of handling sterile products, particularly in oncology pharmacy. These devices prevent contamination during the transfer of medication from one container to another, ensuring the sterility of the product and safeguarding healthcare workers from exposure to hazardous drugs. 

Sterility Testing 

A fundamental component of quality control in sterile compounding is sterility testing. This process involves checking compounded sterile preparations for microbial contamination, ensuring the safety and efficacy of the medication for patient use. The rigorous standards for sterility testing are part of the broader regulatory framework outlined in “The Human Medicines Regulations 2012” (Legislation.gov.uk). 

The distinction between sterile and non-sterile compounding is more than just a procedural difference; it’s about ensuring patient safety and medication efficacy. Adhering to stringent regulations and best practices, from aseptic techniques to cleanroom standards and sterility testing, is paramount in the pharmaceutical industry. By following these guidelines, pharmacists and technicians contribute significantly to delivering safe and effective personalized medication therapies.

Labelling and Packaging Requirements for Compounded Hazardous Medicines

Moving beyond the compounding process, we must consider the critical aspects of labelling and packaging of compounded hazardous medicines. This section will highlight the stringent regulations governing labelling and the importance of accurate and informative packaging in maintaining product integrity and ensuring patient safety. 

Labelling Regulations for Compounded Pharmaceuticals

Compounded pharmaceuticals, particularly cytotoxic drugs used in cancer treatment and other diseases, require stringent labelling regulations. According to the “Human Medicines Regulations 2012“, all medicinal products, including compounded ones, must be clearly labelled. This labelling should include essential information such as the name of the medicine, strength, route of administration, posology, and warnings. The regulations ensure that healthcare professionals and patients can easily identify the medicine and understand its proper use, minimizing the risk of medication errors.

Importance of Accurate Labelling for Patient Safety 

Accurate labelling of compounded hazardous drugs is vital for patient safety. As these drugs can have teratogenic, genotoxic, and carcinogenic properties, improper handling or administration due to mislabelling can lead to severe consequences. The guidelines from “Hospital Pharmacy Europe” highlight the need for well-labelled packaging to prevent occupational exposure and ensure safe administration to patients. Labels must be informative and clear, allowing healthcare workers to recognize and handle these drugs safely.

Packaging Considerations for Product Integrity and Stability

The packaging of compounded hazardous medicines is as crucial as labelling. The “Human Medicines Regulations 2012” stipulate that packaging must not only be secure but also maintain the integrity and stability of the product. Specialized packaging is recommended to prevent material breakage and contain spillage, especially during transport from manufacturers to hospitals. For instance, some manufacturers use moulded plastic containers for cytotoxic agents to confine any contamination in case of spillage. This approach minimizes the risk of exposure to pharmacy storekeepers and other healthcare workers.

Pharmacovigilance and Reporting Adverse Events for Compounding Hazardous Medicines

Introduction to Pharmacovigilance in Compounded Product Safety 

As we near the conclusion, the focus shifts to pharmacovigilance – the watchful eye ensuring the safety of compounded medicines. This segment will discuss the importance of adverse event reporting and how it contributes to improving patient safety and refining compounding practices, thereby playing a pivotal role in the realm of hazardous drug compounding. 

Pharmacovigilance involves the science and activities related to detecting, assessing, understanding, and preventing adverse effects or any other medicine-related problem. This vigilance is particularly vital in the area of compounding hazardous drugs, where the risks are inherently higher due to the nature of the substances involved. The goal of pharmacovigilance in this context is to minimize risks, maximize benefits, and promote the safe and effective use of compounded hazardous medicines. 

Adverse Event Reporting Requirements and Timelines for Compounded Hazardous Drugs

The reporting of adverse events in the context of compounded hazardous drugs is a critical component of pharmacovigilance. It is mandatory to report adverse events electronically, except in exceptional circumstances. For all veterinary medicines, including compounded hazardous drugs, serious adverse events, human adverse reactions, and unintended transmission of infectious agents must be reported on an expedited basis. The Marketing Authorisation Holder (MAH) is responsible for validating all reported adverse events to ensure that the minimum information required is included in the report. These reports should be followed up to obtain additional information relevant to the case as necessary. 

In the UK, for example, serious adverse events in animals and all human reactions occurring must be reported promptly, and no later than 15 calendar days from receipt to the appropriate regulatory body. This expedited reporting is essential for timely intervention and mitigation of risks associated with the use of compounded hazardous drugs.

Contribution of Reporting to Improvement and Patient Safety in Compounding Hazardous Drugs 

The systematic reporting of adverse events in the compounding of hazardous drugs is not just a regulatory requirement but a cornerstone for improving patient safety and drug efficacy. Each reported event provides valuable data that can be analysed to understand better the risks associated with compounded hazardous drugs. This information is crucial for identifying trends, potential safety concerns, and areas for improvement in compounding practices. 

Through diligent reporting and analysis, pharmacovigilance activities contribute significantly to enhancing the safety profile of compounded hazardous drugs. They help in refining compounding processes, improving drug formulations, and developing better guidelines for safe handling and administration. Ultimately, this leads to a higher standard of care and protection for both patients and healthcare professionals who handle these medications. 

Emerging Trends in Pharmaceutical Compounding

In the final stretch of our journey, we explore the emerging trends and challenges in pharmaceutical compounding. This section will delve into the evolving legislative landscape, technological advancements, and the challenges of adapting to these changes. It will underscore the importance of staying updated with regulatory changes and embracing new technologies to enhance the safety and efficacy of compounding hazardous medicines.  

Legislative Trends

The landscape of hazardous drug handling in healthcare settings is undergoing significant transformation, driven by evolving regulatory frameworks worldwide. A notable example is the recent updates to the Clinical Oncology Society of Australia’s position on the safe handling of monoclonal antibodies, reflecting a global shift towards more stringent safety protocols. These changes mirror the principles outlined in the USP General Chapter <800>, which was revised in December 2017 to enhance patient and healthcare worker safety. This chapter provides a comprehensive set of standards for the entire lifecycle of hazardous drugs, from their receipt to disposal, ensuring a holistic approach to safety.  

Technological Trends

The compounding of hazardous drugs is undergoing a significant transformation, thanks to technological advancements. A key development in this area is the use of Closed-System Drug-Transfer Devices (CSTDs), which are instrumental in preventing the release of hazardous drug particles into the environment during their preparation and administration. This innovation enhances safety measures significantly. Complementing this, there’s a growing trend towards automated compounding processes. These automated systems drastically reduce the need for direct contact with hazardous drugs, thereby minimizing exposure risks for healthcare professionals in hospital environments.  

Challenges in Adapting to Regulations and Technology 

Keeping Pace with Regulatory Changes 

Adapting to the dynamic regulatory environment remains a formidable challenge for healthcare facilities globally. The complexity and frequency of updates, as exemplified by regulations like USP <800> and the evolving guidelines in Australia, demand constant vigilance and adaptability. Ensuring compliance necessitates ongoing education and training for healthcare professionals involved in the compounding and handling of hazardous drugs. It’s imperative for healthcare institutions to invest in continuous learning and stay informed about global best practices to effectively navigate these regulatory waters. 

Technological Adaptation 

The integration of new technologies like CSTDs and automated compounding systems into healthcare practices presents certain challenges. One of the primary concerns is the financial aspect, as these advanced technologies typically incur higher costs. Moreover, adopting these new systems and equipment involves a learning curve. It requires healthcare workers to undergo comprehensive training and develop new skills to effectively use these technologies. This adaptation is crucial for ensuring both the safety of the healthcare environment and the efficacy of drug-compounding processes. 

Environmental and Safety Concerns 

The manufacturing and compounding processes for hazardous drugs raise environmental and safety concerns. The challenge lies in implementing sustainable practices that align with regulatory standards while ensuring the safety of healthcare workers and patients. This includes managing waste effectively and minimizing the environmental footprint of compounding practices. 

The Importance of Staying Updated

In the face of these trends and challenges, it is imperative for healthcare facilities and professionals to stay informed about regulatory changes and industry best practices. Regular training, attending seminars, and engaging with professional bodies are essential steps in this direction. Staying updated not only ensures compliance with regulations but also enhances the overall safety and efficacy of compounding hazardous medicines. 

In conclusion, the compounding of hazardous medicines is entering a new era marked by stringent regulations and innovative technologies. Navigating this landscape requires a proactive approach in adapting to regulatory changes and embracing technological advancements. By doing so, we can ensure the highest standards of safety and care in the pharmaceutical industry, ultimately benefiting both healthcare professionals and patients alike. As we move forward, it is crucial for all stakeholders to collaborate and share knowledge, ensuring that the compounding of hazardous medicines continues to evolve in a safe, efficient, and compliant manner. 

 

Maximizing Efficiency and Safety in Healthcare: Real Life Case Studies on Cost Savings with Closed System Drug Transfer Devices (CSTDs) 

CSTDs have been instrumental in transforming medication safety in healthcare facilities. As the industry increasingly focuses on the well-being of healthcare professionals, these devices are recognized for their role in optimizing resource management, reducing product waste, and addressing occupational health risks. According to NIOSH (National Institute for Occupational Safety and Health)1, CSTDs ensure safe, contained drug transfers, minimizing exposure to hazardous drugs and offering significant financial benefits. 

CSTDs: Boosting Occupational Safety and Cutting Costs in Pharmacy Compounding

In healthcare environments, especially during the compounding process, Closed System Drug Transfer Devices (CSTDs) play a crucial role in minimizing the risks of hazardous contamination. They establish a secure, airtight connection between drug vials, syringes, and IV bags, effectively preventing exposure to harmful aerosols and vapors. By incorporating physical barriers, CSTDs ensure the containment of hazardous drugs, thereby significantly reducing the risk of exposure to hazardous particles.  

Research shows a reduction in contamination risk from 26.4% with standard isolators to 12.2% with CSTDs2, enhancing safety measures for pharmacists, nurses, and other healthcare professionals. 

To further illustrate the impact of CSTDs, this paper explores real-world case studies where pharmacies and compounding centers have successfully implemented these systems, leading to substantial financial savings alongside enhanced safety measures. 

Relevant Cost Reductions Proven by Extended Beyond Use Date (BUD): Case Studies at Mount Sinai and Bronson Battle Creek

Chemotherapy healthcare team

The implementation of Closed System Transfer Devices (CSTDs) in healthcare settings, particularly in outpatient cancer centers, has shown significant potential for cost savings by reducing medication wastage. Notable examples come from Mount Sinai Hospital – New York, USA  and Bronson Battle Creek (BBC) Cancer Care Center – Michigan, USA. 

At Mount Sinai Hospital, by extending the BUD (Beyond Use Date) of single-dose vials from 6 hours to 7 days, as approved by the FDA in the case of Equashield, the hospital could significantly reduce the amount of discarded medication. This led to substantial savings for six agents, enough to offset the cost of using Equashield solution to comply with USP 800 standards.3 The figures were impressive, showing an annual cost reduction of $530,000, underscoring the economic advantages gained from incorporating the CSTDs.4 

Similarly, Bronson Battle Creek Cancer Care Center (BBC) also implemented a CSTD, aiming to decrease waste and offset the cost of CSTDs implementation in a comprehensive cancer care center. The results demonstrated financial efficiency in reducing drug wastage, applicable in both large university hospitals and smaller community healthcare settings3

Relevant Cost Reductions Proven by Extended Beyond Use Date (BUD): Case Studies

More Real-Life Examples: Demonstrating Financial Gains with CSTDs and Automated Drug Compounding 

Recent research, including one conducted by the Pharmacy Department of the Centre Regional de Lutte Contre le Cancer Léon Bérard5, has shown that Equashield CSTDs (closed system transfer devices) minimize contamination risks compared to traditional methods, leading to safer work environments, reduced direct contact with hazardous drugs, and significant financial benefits6.

The study, “An economic evaluation of vial sharing of expensive drugs in automated compounding,”7 highlights the economic advantages of an innovative approach to drug compounding. By implementing an automated compounding process with a vial-sharing strategy, significant cost savings were achieved. This method, contrasting with traditional manual compounding, led to avoiding drug wastage during the automated process. The study revealed that over six months, the cost of drug wastage for 1001 preparations of rituximab, pemetrexed, bevacizumab, and trastuzumab combined, amounted to €34.133, €46.688, and €88.255 for different manual compounding scenarios. In contrast, the automated compounding with vial sharing resulted in substantial savings, with an estimated total cost reduction exceeding €280.000 between 2017 and 2021. This approach not only presents an economic advantage but also contributes to environmental sustainability by minimizing drug wastage. Additionally, automated compounding saves valuable staff time, enhancing overall efficiency alongside its other benefits.

Reducing Liability and Undesired Healthcare Costs in Drug Compounding 

CSTDs (closed system transfer devices) have emerged as key players in mitigating potential liability and contributing to cost-effective practices. They provide a closed and secure environment, reducing exposure to hazardous drugs and minimizing potential financial burdens. A case study in Genoa8 found that using Equashield during drug compounding resulted in no detectable levels of gemcitabine, a cytostatic drug used in chemotherapy, highlighting both safety benefits and potential cost savings. 

Before the implementation of Equashield II, the study found detectable levels of GEM contamination in various samples, including on operators’ gloves, suggesting that the preparation systems used at the time were not fully sealed. This was evident in the results, where GEM was detected in several samples, indicating a risk of occupational exposure to the drug. 

Reducing Liability and Undesired Healthcare Costs in Drug Compounding 

 

After the introduction of Equashield II, the study observed a significant change. The subsequent monitoring from 2020 to 2021 showed that gemcitabine was not present at detectable levels in any of the evaluated samples when using the Equashield II system. This contrasted with the results obtained using the TexiumTM/SmartSiteTM system, where GEM dispersion was still observed after compounding, with positive samples ranging from 9-23%. 

The absence of detectable levels of GEM in samples when using Equashield II indicates that this CSTD was effectively able to eliminate spills and leakage during the compounding of gemcitabine, thereby significantly reducing the risk of contamination and exposure. This result underscores the effectiveness of Equashield II in creating a safer environment for healthcare workers by minimizing the potential for hazardous drug exposure during the compounding process. 

By preventing exposure-related health problems, CSTDs such as Equashield help to reduce sick leave costs and potential legal consequences. As such, these devices play a vital role in protecting healthcare facilities against both safety and financial risks. 

To conclude our exploration of real-life examples and case studies, let’s summarize the key advantages of CSTDs that have been consistently observed across various healthcare settings. 

Summarizing the Success: Key Advantages of CSTDs in Pharmaceutical Compounding 

The integration of CSTDs has significantly improved staff confidence in medication administration. Healthcare workers felt safer and more confident in handling hazardous drugs, knowing that the risk of exposure was minimized. 

Streamlined operations

The use of CSTDs can lead to faster medication preparation and administration. These devices are designed to minimize connections and disconnections during compounding, ultimately saving valuable time and reducing costs. 

Minimize the risk of exposure to hazardous drugs

CSTDs offer the potential to reduce direct exposure of healthcare workers to hazardous drugs by creating a closed environment. The impact is significant: one study found that contamination was reduced from 26.4% with traditional methods to 12.2% with CSTDs, resulting in reduced sickness absence and a safer workplace.9 

Improved productivity

A study at Nebraska Methodist Hospital found that CSTDs significantly improved the time efficiency of compounding. The task was completed in 36.4 seconds with EQUASHIELD, one of the CSTDs evaluated, compared to 87.7 seconds with other CSTD brands and 63 seconds with traditional needle and syringe methods.10 

Innovations Lead to Cost Savings in Drug Compounding: The Financial Impact of CSTDs and Automation

Reflecting on the case studies and real-life examples, it’s clear that the compounding of hazardous drugs is evolving with a focus on innovative solutions like Closed System Transfer Devices (CSTDs) and automated compounding systems. These technologies not only mitigate the risks associated with hazardous drugs but also lead to significant cost savings. For instance, the study “The Future of Hazardous IV Drug Preparation is Here” 11 highlights that the use of automated systems can substantially reduce operational expenses. It’s estimated that savings from the reduced waste of partial vials can amount to $70.000 annually while avoiding medication errors can save approximately $18.720 per year. Additionally, the elimination of costs associated with CSTDs, estimated at $117.000 annually for both prescription and nursing doses, underscores the financial efficiency of these technologies. This trend towards automation and CSTDs is pivotal in enhancing healthcare safety and ensuring the financial viability of pharmacies. 

Conclusive Insights: Embracing CSTDs and Automation for Safer, More Cost-Effective Drug Compounding 

The series of case studies and real-life examples we’ve explored provide valuable insights into the evolving landscape of drug compounding, particularly with hazardous drugs. The key takeaway is the significant role of Closed System Transfer Devices (CSTDs) and automated compounding systems in driving cost savings and enhancing safety in healthcare settings. 

Cost Savings through Extended BUD and Reduced Wastage

The cases of Mount Sinai Hospital and Bronson Battle Creek (BBC) demonstrate how extending the Beyond Use Dating (BUD) of single-dose vials, as enabled by CSTDs like Equashield, can lead to substantial cost savings. By minimizing medication wastage, these healthcare facilities have shown annual cost reductions, highlighting the economic benefits of CSTD implementation. 

Enhanced Safety and Efficiency

The integration of CSTDs has been shown to not only improve safety by reducing contamination risks but also to enhance operational efficiency. This dual benefit is crucial in a healthcare environment where both safety and cost-effectiveness are paramount. 

Innovative Approaches in Compounding

Studies like “An economic evaluation of vial sharing of expensive drugs in automated compounding” underline the financial and environmental advantages of innovative compounding methods. Automated compounding with vial sharing, in contrast to traditional manual methods, has resulted in significant time and cost savings while reducing drug wastage.  

Mitigating Liability and Health Risks

CSTDs have also been instrumental in mitigating potential liability and health risks associated with the compounding and administration of hazardous drugs. By providing a safer working environment, they help reduce healthcare costs and potential legal consequences. 

In conclusion, the adoption of CSTDs and automated compounding systems represents a strategic move towards more efficient, safe, and cost-effective drug compounding practices. These innovations not only enhance the safety of healthcare professionals but also offer substantial financial benefits, making them a valuable addition to any healthcare facility’s medication management strategy. 

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Discover the Financial and Safety Benefits of CSTDs

Closed System Transfer Devices (CSTDs) play a critical role in protecting the health of pharmacy staff during hazardous drug compounding. Each year, over 8 million healthcare professionals in the US and 12 million in Europe face the risk of exposure to hazardous drugs, a concern that has been extensively studied. (1)(2) CSTDs, with their advanced design, serve as powerful barriers, preventing exposure to dangerous drugs and reducing contamination. They also minimize waste and enhance the well-being of the staff working in hospitals and pharmacies.    

In the following sections, we will explore the significant impact of CSTDs on the compounding process.

The Key Benefits of Using CSTDs in Pharmaceutical Compounding 

A closed-system drug transfer device effectively minimizes contamination risks in healthcare settings.

Prioritizing Safety with Closed-System Transfer Devices

Closed System Transfer Devices (CSTDs) have become essential tools in drug compounding for both pharmacists and nurses, in order to address the issue of hazardous drug exposure. According to NIOSH, a CSTD mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system.(3) By creating an airtight connection between drug vials, syringes, and IV bags, they successfully prevent the release of harmful aerosols and vapours, significantly reducing the risks associated with direct contact, skin exposure, and inhalation. (4)

More Occupational Safety with CSTDs

CSTDs employ various technologies, each offering different levels of safety. Physical barriers establish a closed system, containing hazardous drugs, while air-cleaning technology filters out particles from the air. (5) This rigorous containment strategy provides a protective environment for healthcare staff, minimizing the potential long-term health risks associated with hazardous drugs.

Reducing Contamination Risks and Occupational Exposure to Chemotherapy Drugs 

One standout benefit of a closed-system drug transfer device is the significant reduction in contamination hazards for healthcare workers. Research shows a substantial decrease in hazardous drug exposure when CSTDs are the preferred medical devices in use, with a contamination rate of 12.24% compared to 26.39% with standard isolators. (6) By adopting CSTDs, pharmacists, nurses, clinicians, and other staff can enhance safety measures, creating a safer and more secure healthcare setting. 

Contamination Control in Chemotherapy Drug Compounding: CSTDs vs. open systems

In this section, we will compare CSTDs with their market alternatives. We will shed light on their distinctive features and provide guidance on the most suitable choice for various drug-compounding scenarios.

CSTD products 

These devices maintain a sealed environment throughout the drug preparation process. Equipped with vial adapters and other components, CSTDs ensure that hazardous drugs are contained, protecting pharmacy staff. Particularly for dangerous drugs, CSTD performance is invaluable, effectively preventing the release of aerosols or vapours.

Open Systems

Open systems possess a degree of permeability due to their inherent lack of a complete seal. They are simpler and often more affordable, making them suitable for drugs with a lower contamination risk. However, their protective capabilities do not match those of CSTDs. 

In conclusion, CSTDs offer enhanced protection, especially for hazardous drugs. The choice between CSTDs or alternative solutions should be based on the nature of the drug (hazardous vs non-dangerous), potential staff risks, and regulatory standards, always with a focus on safe and secure compounding. When compounding hazardous drugs one should always use CSTDs as the devices are the only ones able to ensure safety during the process.

The Mastery of Contamination Prevention 

In addition to their numerous benefits, CSTDs excel at preventing contamination. Their design provides a dual defence mechanism: they prevent environmental contaminants from entering the system and ensure that hazardous drug particles and vapours are securely sealed within. This robust shield significantly reduces the danger of accidental contamination, setting CSTDs apart in terms of efficiency and protection for healthcare professionals and patients alike.

How do CSTDs prevent drug spills and leakage?

Furthermore, CSTDs offer impeccable protection against drug spills and leakage. They accomplish this through a foolproof mechanism that restricts the entry of environmental contaminants and securely contains hazardous drugs or vapours. Once activated and sealed, the CSTD system prevents any inadvertent entry or exit, including bacteria or particulate matter. This level of precision safeguards the compounding process from unintended breaches, highlighting the unparalleled capability of CSTDs in ensuring the integrity of drug handling. 

The Financial Benefits of Transfer Devices with Closed Systems

In the world of healthcare, financial considerations are just as important as security. That’s why we’re taking a closer look at the economic advantages of CSTDs. This section explores how CSTDs save money and reduce waste, highlighting the long-term financial benefits of investing in these devices in the healthcare sector. 

Using a Drug Transfer Device Enables Cost Savings through Waste Reduction

Using CSTDs offers significant cost savings by minimizing drug waste. By providing protection against microbial growth, the use of the vial can be extended, allowing for longer periods of use beyond the original expiration date. Studies show that implementing CSTDs reduces drug waste by an average of 72.5%. (7)  This not only conserves valuable medications but also has a positive environmental impact by reducing the disposal of hazardous drugs. 

Optimizing Drug Compounding with CSTDs

Efficiency studies have demonstrated that the closed systems extend the sterility of single-use vials, enabling the practice of vial sharing which significantly cuts down the volume of drugs thrown away after just one use. Remarkably, studies highlighted that CSTDs can preserve vial sterility for as much as seven days, with contamination rates remaining negligible up to 30 days, leading to considerable financial savings due to reduced drug wastage (8). 

These devices not only ensure precision in medication measurement and dispensing, leaving minimal residue, but their design also prevents any medication leaks and drips, maximizing every drop. The controlled air pressure and accurate dosing provided by CSTDs also play a crucial role in averting the risks associated with overfilling or underfilling vials, which further trims down waste. Such efficiency has been shown to provide substantial economic benefits. Cost savings from integrating CSTDs into healthcare practices range from 7-15% on overall drug and device expenses. This can translate into annual savings of around £480,000 by recovering an average of 57% of unused drugs from vials, with Hungarian hospitals reporting noteworthy savings, particularly with costly parenteral biological agents (9). Collectively, CSTDs make a compelling case not only for their role in reducing drug waste but also for optimizing healthcare resources through their economic use. 

Enhancing Results by Integrating CSTDs with DVO

Combining CSTDs with Drug Vial Optimization (DVO) techniques provides a comprehensive approach to protection and efficiency. While CSTDs ensure a secure drug-handling environment, DVO maximizes medication extraction from vials with minimal residue. This combination not only protects healthcare professionals but also offers long-term financial benefits, establishing a sustainable and cost-effective solution for patient care and financial health. 

Factors that influence the vial savings when compounding hazardous drugs with CSTDs and DVOs 

Calculating vial savings during the preparation of cytostatic drugs with CSTDs and Drug Vial Optimization (DVO) depends on multiple variables, such as the drug specifics, equipment, and compounding procedures. Key considerations include: 

Drug concentration: Higher concentrations may yield more doses per vial, enhancing DVO savings. 

Vial size: Bigger vials could result in more savings by optimizing usage. 

Vial cost: Selecting vials should be cost-effective, balancing the price per millilitre with potential waste. 

Shelf life: Consider the drug’s stability post-mixing to prevent waste from expiring drugs.  

Compounding efficiency: Properly trained staff using CSTDs and DVO can minimize errors and waste. 

Regulatory adherence: Comply with all regulations to ensure safe compounding practices. 

Demand analysis: High demand for a drug could mean significant savings through vial optimization. 

DVO efficiency: The efficacy of the DVO technology used affects the amount of extractable doses. 

Drug properties: Consider the compounding impact of drug characteristics like viscosity and solubility. 

Staff education: Skilled staff using CSTDs and DVO technology can maximize their well-being at the workplace while increasing cost savings. 

Long-Term Cost Savings: CSTDs vs. Alternative Solutions 

In addition to the economic and sterility benefits presented earlier, CSTDs address also the financial consequences of contamination in healthcare settings. Exposure to hazardous drugs poses risks to healthcare professionals and patients, resulting in significant financial strains. These strains include costs associated with potential medical expenses due to staff harm, and the management of contamination fallout. Using CSTDs in drug compounding provides a key solution for such issues and ensures financial profitability in the long term. 

The Ripple Effect: The Costs and Consequences of Staff Exposure to Hazardous Drugs 

Human errors in healthcare settings can have detrimental effects on staff, leading to a series of costly repercussions. Immediate expenses include medical treatment, testing for exposure to hazardous drugs, and time off work. Furthermore, staff illnesses can result in workforce shortages, requiring the need for temporary hires and additional expenses. These issues disrupt operations and drive up costs. Additionally, if patients are adversely affected, legal and compensation expenses may arise. Given these financial strains, it is crucial to implement preventive strategies to address the broad impact of staff exposure incidents. (10)

Mitigating Contamination Costs with CSTDs: A Proactive Approach

By using Closed-System Drug-Transfer Devices (CSTDs) to ensure a sealed environment during drug preparation and administration, the risk of staff contamination can be significantly reduced. This helps minimize immediate medical expenses related to exposure treatments, prevents operational disruptions, and eliminates the likelihood of legal and compensation claims. Implementing CSTDs demonstrates a proactive commitment to healthcare safety, protecting the well-being of healthcare professionals while also ensuring cost-effectiveness in operations. 

Maximising Your CSTD Return on Investment by Investing in Staff Education

Investing in staff education for the proper use of Closed System Transfer Devices (CSTDs) is paramount in the healthcare sector, both for ensuring safety and enhancing financial outcomes. Effective training equips staff with the necessary skills to operate, maintain, and create efficient protocols for CSTDs, leading to fewer errors, reduced contamination risks, and improved chemotherapy administration. This not only advances patient care and satisfaction but also significantly increases return on investment (ROI) by minimizing costly mistakes such as drug spillage and avoiding needlestick injuries, which can cost between £10,000 to £620,000 alone, according to a report in Scotland. (11) Hence, comprehensive training is a strategic investment that yields long-term financial benefits by optimizing medication use and reducing healthcare risks. Equashield provides free training for all healthcare professionals interested in improving occupational safety and well-being in hospitals and pharmacy environments.

Choosing the Right CSTD: Factors to Consider 

Selecting the appropriate CSTD is not as simple as choosing any other item. Comparing CSTDs in a real-world setting requires thorough education for all staff involved in testing. Here are the key aspects to consider when selecting a CSTD

Safety: When it comes to handling hazardous drugs, the safety of healthcare personnel is the top priority. Utilizing a completely closed CSTD is crucial to provide the utmost level of protection against the risks linked to exposure and contamination.

Compatibility: Ensure the CSTD is compatible with all tubing and pump equipment used in your facility. 

Effectiveness: Evaluate the device’s ability to prevent work environment contamination and exposure to high vapour concentrations when disconnecting IV tubing after infusion. 

Ease of use: Choose a device that is user-friendly and does not require extensive training. 

Cost: Consider the device’s total cost of ownership and its fit within your facility’s budget. 

Reliability: Select a device with a proven track record of success and reliability. Those designed with the closed-back syringe tend to be the safest and show the highest CSTD performance.

Ensuring Compatibility with Existing Regulations and Protocols

Before integrating a Closed System Transfer Device (CSTD) into your healthcare facility, it is crucial to ensure it aligns seamlessly with your country’s existing protocols and regulations. Different regions may have specific guidelines for medication safe handling and increased risk exposure. Verify that the chosen CSTD meets the regulatory requirements and healthcare protocols in your area. This step is vital for maintaining compliance, enhancing patient safety, and streamlining your drug transfer processes.

 

EQUASHIELD Changed the World For Me

Mark Stanfield has had a diverse career path, starting as a musician and later working in Hollywood producing television commercials. However, after the events of September 11, he felt a calling to make a difference in people’s lives and found his path as an oncology pharmacist.

In 2017, he was diagnosed with stage four lung cancer, which led him to question the safety of certain medical equipment at his workplace. Concerned about the potential harm to others, he embarked on a mission to improve safety in the medical field by identifying a closed system transfer device (CSTD) that effectively prevents vapor escape. He discovered that EQUASHIELD is the best CSTD to cover all routes of exposure. Despite his personal health struggles, Mark remains resolute in his commitment to fearlessly living life and promoting safe compounding practices for fellow healthcare professionals.

Mark’s full story

EQUASHIELD Syringe Unit

FDA Clearance of EQUASHIELD® Syringe Unit for Full Volume Use

We are thrilled to announce that the EQUASHIELD® Syringe Unit has received additional FDA clearance for full volume use1. This achievement marks a significant milestone for our company, as we celebrate our fifth consecutive year of being the most used CSTD in the USA. We firmly believe that our innovative product design will revolutionize the way hazardous drugs are handled, offering unparalleled safety and efficiency.

Compared to Other Syringes on the Market 

Many institutions adhere to guidelines that limit the fill volume of standard syringes to three-quarters when handling hazardous drugs (OSHA, ASHP) to prevent loss of the plunger2,3. Our EQUASHIELD® Syringe Unit, however, eliminates this risk, preventing vapor escape and plunger contamination. The design allows you to use the most accurate syringe size possible for compounding and administration4.  

Introducing the Unique EQUASHIELD® Syringe Unit 

EQUASHIELD® Syringe Unit, a barrier type CSTD, stands out from its competitors with its one-of-a-kind closed-back design and bonded connector. This innovative design effectively eliminates more routes of hazardous drug exposure than alternate systems, preventing vapor escape and plunger contamination. The encapsulated plunger of the EQUASHIELD® Syringe Unit cannot be detached from the barrel, ensuring the safe usage of the entire Syringe Unit volume.

Benefits of Full-Volume Use 

Full-volume use of the EQUASHIELD® Syringe Unit has multiple benefits:  

  • Cost reduction: Utilize fewer syringes for compounding and administering a dose, thanks to the full volume utilization of each syringe. In combination with the full volume use and largest EQUASHIELD® syringes being 35mL and 60mL, contribute to major cost savings compared to regular off the shelf syringes.   
  • Reduced strain: Experience less strain due to minimized repetitive motion.
  • Save time: Compound and prepare doses more efficiently with fewer syringes, leading to significant time savings. 
  • Waste reduction: Decrease waste in both compounding and administering doses with optimized syringe usage. 

Consider the following example to illustrate the potential cost savings:

EQUASHIELD significantly reduces syringe usage, streamlining the process with just 1 Syringe Unit. In contrast to other CSTD’s that often require 2 syringes + 2 or more injectors/connectors for the most common drug. This streamlining ensures efficiency and cost-effectiveness in your drug handling practices.

A Safer and More Efficient Solution 

The EQUASHIELD® Syringe Unit was created with your safety at the forefront of our minds. We understand the potential risks involved with handling hazardous drugs, and we believe that our unique design offers a safer solution. The FDA clearance is a testament to the commitment we have in ensuring our products are safe and reliable.

In addition to safety, the EQUASHIELD® Syringe Unit offers efficiency. By allowing full-volume use, we help streamline your processes, reducing waste and maximizing your resources. This results in a cost-effective solution for your medication compounding and administrating needs.

Embrace Safety and Efficiency with the EQUASHIELD® Syringe Unit 

For over a decade, through our innovative design and commitment to safety, we have created a product that stands out in the industry. The EQUASHIELD® Syringe Unit is more than just a syringe; it’s a safe, efficient, and cost-effective solution for handling hazardous drugs. As we mark this FDA clearance, we look forward to continuing to provide you with the highest quality products that meet your needs.

Syringe plunger contamination by hazardous drugs: A comparative study

Introduction

Our institution administers thousands of monthly chemotherapy doses, so we were very early adopters of both USP7971 and NIOSH recommendations. 2 We had developed and implemented policies and procedures outlining safe and appropriate procedures for handling oncological agents, the utilization of cleanrooms and biological safety cabinets, personal protective equipment (PPE), and many other protective measures. Those policies and procedures included the utilization of the Phaseal Closed System Transfer Devices (CSTD) with Becton Dickinson (BD) syringes. Three years ago, we replaced the Phaseal devices with a new CSTD, Equashield. The design, simplicity, ergonomics, and the potential for decreasing our hazardous waste we felt offered an advantage over the BD Phaseal products. Favier et al.,3 in a peer-reviewed study, examined the potential for syringe plunger contamination during routine drug preparations at hospital pharmacies. This study confirmed and quantitated that considerable contamination from cyclophosphamide did occur on the BD syringe plungers. This study included wipe test sampling of syringe plungers from syringes that were purposely operated with repeated withdrawal and re-injection cycles of cyclophosphamide to simulate repeated use. The study also performed wipe test sampling of syringes collected after normal use during a pharmacy routine work day. Both groups of syringe samples were found to be contaminated. This previously undetected route of exposure poses a problem as it has identified another potential source of contamination of gloves and the work environment, which increases the risk of exposure to the pharmacy staff, nurses, patients, and their families. These findings highlight the urgent need for improved safety measures in healthcare settings. An essay on nursing should address this issue, emphasizing the importance of proper handling and disposal of hazardous substances to protect both healthcare professionals and patients. A few years later, a research laboratory specializing in antineoplastic agents and environmental contamination repeated the plunger contamination study.4 This study included Equashield syringes in addition to BD and Terumo syringes. This study confirmed the findings of the previous study3 with high contamination rates of up to 0.5 mg cyclophosphamide found on both the BD and Terumo syringe plungers. Since both manufacturers, BD and Equashield have claimed to have made enhancements in the performance of their products, we asked Equashield to sponsor a similar comparative study at our institution. Equashield agreed and a small study was developed that would test the levels of contamination of the BD syringes with Phaseal CSTD devices against those from Equashield.

Karmanos Cancer Center, Detroit, MI, USA
Corresponding author:
Stephen T Smith, Department of Pharmacy, Karmanos Cancer Center,
4100 John R. Street, Mailcode: WE01PH, Detroit, MI 48201, USA.
Email: [email protected]

Method

The study included 11 Equashield 60 mL syringe units and 12 BD PlasticTM 60 mL syringes. The Equashield syringes are a stand-alone closed system that includes factory built-in closed pressure equalization system and dry connectors. The BD syringe is a traditional single use syringe with a luer lock tip manually attached to the appropriate Phaseal dry connector (Injector). The closed pressure equalization system is built-in the Phaseal vial adapter (Protector).

The difference between the BD and the Equashield syringes is shown in Figures 1 and 2. The BD syringes have an open syringe barrel and a regular four ribs plunger structure. The Equashield barrel is sealed by a lid and the plunger is a small diameter metal rod that can move through the lid. A seal, seated in the center of the lid, seals the rod and ensures airtight operation of the syringe.

Four Equashield Vial Adaptors (VA-20) and four Phaseal Protectors (P-50) were attached to eight cyclophosphamide 2 g vials, respectively. Each vial was reconstituted with 100 mL of standard sodium chloride 0.9% solution to a final concentration of 20 mg/mL. There were eight syringes and adaptors utilized of each system to complete the transfer in 50 mL aliquots into the drug vials.

The syringes were divided into three equal groups for the Equashield and BD syringes, with a vial of the reconstituted cyclophosphamide designated for each group with the exception of the last group which received 2 vials each. A 50 mL aliquot of cyclophosphamide was drawn into each syringe and then injected back into the cyclophosphamide vial. This drug transfer procedure was immediately repeated twice for the syringes in group 1, four times for the syringes in group 2, and eight times for the syringes in group 3. Only 50 mL were drawn into the syringes to remain within the manufacturers’ guidelines of use and minimize the potential for a possible spill. The same withdraw and reinjection processes were applied to the syringes which were similar to those one would encounter during a routine pharmacy compounding procedure.

After the completion of the drug transfers with the Equashield and BD Phaseal syringes, the plungers were retracted back to the nominal syringe marking and a wipe test of the exposed plunger was done.

A wipe sample was taken from the biological safety cabinet work surface at the commencement of the study to rule out any possible contamination prior to the study. The size of the wiped surface was 1 ft2 (930 cm2).

The services of ChemoGloTM (Chapel Hill, North Carolina), a specialized third-party laboratory, were used to accurately quantify trace amounts of cyclophosphamide on the syringe plungers and work area sample. The ChemoGloTM assay has a low detection level of 10 ng (1 109 ) per wipe sample and is simple to use. The assay is optimized for wipe sampling of any surface area up to 1 ft2 (930 cm2), which is optimal for wiping the smaller surface of the syringe plungers. The quantification of cyclophosphamide is, therefore, the total quantity of cyclophosphamide in nanograms found on a plunger/wipe sample.

Four kits were utilized for a total of 24 wipe samples (each kit consisting of six wipes samples) which were completed in accordance to the procedures outlined by ChemoGloTM.

The wipe samples were taken using the ChemoGloTM swab with absorbed solution. The plungers were retracted back to the nominal syringe marking and the exposed plungers wiped thoroughly with the wet swabs. After the completion of the wipe sampling, the swab was placed in a dedicated labeled container. Since each wipe sample consists of two swabs and solution containers, this process was repeated for the secondary swab sampling.

All 48 containers with the wipe samples (two containers for each syringe 23 syringes, and two containers for testing the work surface) were sent overnight to ChemoGloTM laboratory for the performance of sample extraction and analysis with LC-MS/MS technology.

The test was performed in a Thermo Class II, A2 Biological Safety Cabinet by an experienced chemotherapy-certified pharmacy technician, proficient with the use of both the Equashield and Phaseal CSTDs. The working area was cleaned in accordance to our facility’s standard procedure prior to initiation of the study. To isolate the study and exclude any foreign source of contamination that may influence the results, the drug vials were cleaned with IPA pads and only materials which are required for the study were kept in the hood. Large absorbent pads were used to cover the whole work area. The pads were replaced and the gloves changed before working with each group of syringes.

Figure 1. The BDÕ syringe (left) and the EquashieldÕ syringe (right).

Syringe plunger contamination by hazardous drugs: A comparative study

Figure 2. The EquashieldÕ syringe (top) and the BDÕ syringe (bottom).

Syringe plunger contamination by hazardous drugs: A comparative study

Table 1. Amounts (ng) of cyclophosphamide on the tested syringe plungers.

Syringe plunger contamination by hazardous drugs: A comparative study

Figure 3. Contamination levels (ng) of cyclophosphamide (CP) on the tested syringe plungers.

Results

Results demonstrated significant cyclophosphamide contamination levels on 11 out of 12 BD syringes, whereas all 11 Equashield CSTDs had undetectable concentrations. The 1 ft2 (930 cm2 ) work area wipe showed minor contamination of 16.82 ng, considered to be close to the lower limits of detection level (LLQ) (Table 1).

Statistical assessment

We regard this study to be a small-scale pilot study with the intent of reviewing the two CSTDs that we were familiar with. We had little preliminary data to determine the study’s sample size; therefore, an assumption of 11 syringes was made based on previous studies.3,4 The results confirmed the assumption and show that the average contamination level for the BD plungers was ¼ 1622 ng with a variant, 2 ¼ 331 ng2 . Assuming a normal distribution, CP ~ N(µ, σ2 ), the average contamination level on the BD plunger was greater than 1228 ng, with a confidence level of 95%. That is to say, that if we used an unlimited number of syringes, we could be 95% sure that the averaged contamination level would be above 1228 ng. Since the technology is limited to detect and quantify between 10 ng and 2000 ng, for the statistical analysis of the results, we assumed that when the contamination was above the technology’s detection limit, we regarded it to be 2000 ng understanding that the true level of contamination may exceed that value several-fold. This has already been documented in previous studies 4,5 using HPLC-MS/MS analysis method (Figure 3).

The lower limits of detection (LLQ) for these assays are 10 ng. Quantities that are less than the LLQ are defined as non-detectable (ND). The upper limits of detection for these assays are 2000 ng. Quantities that are greater than 2000 ng are defined as > 2000.

Discussion

The contamination levels found on the standard BD syringe plungers confirm previous studies.3,4 This contamination highlights the potential of a significant source of low-level exposure for healthcare workers
while they prepare and handle hazardous drugs during their routine workday. It is suggested that the staff’s gloves come into contact with the syringe’s contaminated plungers then in turn, touch other surfaces such as the work area, the prepared IV bags which are distributed to patient care areas, and so forth, thus contaminating the entire work environment and increasing the potential of exposure.

Following the results of previous study,4 where contamination was also found on tested Terumo syringes, it is most likely that BD syringes generally represent standard syringes of other manufacturers as well.
Furthermore, the contamination on standard plungers is expected regardless of use of a CSTD or traditional methods when handling hazardous drugs.

Similarly, our results demonstrated no detectable level of contamination on the Equashield syringe plungers which supports previous findings3,4 as well as the NIOSH recommendations2 that endorse the use of CSTD which mechanically prohibits the escape of hazardous drug or vapor concentrations outside the system in order to minimize exposure to hazardous drugs.6

We believe that cyclophosphamide infiltrates on to the plungers of standard BD syringes by reacting and creating a layer on the inner walls of the syringe barrel.

The very minimal distance or direct contact between the plungers to the contaminated walls ‘‘allows’’ cyclophosphamide to ease its way on to the plunger. The typical squeezing of the barrel, bending or twisting of the plunger during real use conditions often creates a direct contact between plungers to the contaminated walls, thereby allowing transfer of contamination. It has been shown that the safety measures adopted through the Equashield design address the risk of plunger contamination7 by preventing contact and ensuring greater distance between the Equashield plunger rod and the syringe barrel in this contained CSTD.

Finally, the contamination levels of cyclophosphamide found on the work area sample were close to the LLQ and may therefore be considered of little consequence.

Conclusions

This study has confirmed the hazards associated with standard syringes and the importance of using appropriate closed system syringes during all preparation and handling stages of hazardous drugs, in order to significantly reduce healthcare workers’ exposure to contaminated surfaces and work environments. It is suggested that in light of this study, and the medical literature which it echoes, further investigation and consideration are required, and more rigorous regulations and policies should be established in this area in order to further minimize risks and optimize the safety of healthcare workers.

Funding

This study was partially sponsored by Equashield.

Conflict of interest

The authors have no conflict of interest to disclose.

Use of a closed system drug-transfer device eliminates surface contamination with antineoplastic agents

Background

Harmful effects from workplace exposure to antineoplastic agents were first described in the 1970s.1 Noted risks of handling these agents by nurses and other healthcare personnel include damage to DNA, infertility and a possible increased risk of cancer.2–8

The use of personal protective equipment (PPE) when handling chemotherapy has been recommended by The Occupational Safety and Health Administration (OSHA) since 1986.9 Pharmacists, pharmacy technicians and nurses risk exposure to antineoplastic agents when preparing and administering these drugs. Many studies have documented surface contamination with these agents in healthcare institutions10–14 and a recent study noted that doxorubicin can penetrate nitrile gloves.15 Additionally, hazardous drugs have been found in the urine of healthcare workers who prepare or administer chemotherapy.11,13,16 PPE is therefore used during preparation and administration in order to reduce exposure during these times. 

Prior studies have shown surface contamination outside of the biological safety cabinet.10–14 Healthcare workers are likely to come in contact with contaminated surfaces when not wearing PPE. Minimizing environmental contamination with antineoplastic agents is imperative to protect workers from the harmful effects of these agents.

Closed system drug-transfer devices (CSTD) can reduce exposure of health care workers to harmful agents. Numerous reports have been published that describe the effectiveness of CSTDs at decreasing surface contamination and exposure of healthcare personnel after implementation of the devices.13,14,16–21 The National Institute for Occupational Safety and Health (NIOSH)22 and The United States Pharmacopeia’s current USP 79723 standards recommend the use of CSTDs when preparing and administering chemotherapy in addition to the use of PPE.

Several CSTDs are marketed for use with cytotoxic agents. A recently published study of 22 United States hospitals noted that surface contamination was reduced significantly after the implementation of a well-known CSTD.14 However, the CSTD product used in this study has yet to be evaluated in the workplace setting. Testing of surfaces in the workplace for contamination after implementing the CSTD is important to validate the utility of the product.

Testing for surface contamination with cytostatic agents in the cancer center was completed for two reasons. An evaluation of the effectiveness of the standard method for preparing (Chemo Dispensing Pin, B. Braun Medical Inc.) and administering chemotherapy was necessary. The second reason was to evaluate whether the CSTD would decrease the level of surface contamination at various locations within the cancer center 1 year after implementation.

This study was conducted at an ambulatory cancer chemotherapy infusion center that is part of a large health-system in the Midwest of the United States. Within the center is a 21-chair infusion suite with a dedicated pharmacy preparing the chemotherapy products to be administered in the infusion suite. The cancer center has approximately 16,500 chemotherapy visits per year.

At the cancer center, the pharmacy technicians prepare all doses of chemotherapy under the supervision of the pharmacist. Pharmacy staffing consisted of two fulltime pharmacists and two full-time certified pharmacy technicians. An estimated 450 g of cyclophosphamide and 2600 g of 5-fluorouracil are prepared each year. The pharmacy has one biological safety cabinet for the preparation of all medication doses. The biological safety cabinet is a Class II Type A/B3 and has been in use for 10 years. 

Table 1. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples after the use of safety pins and without any prior cleaning (baseline contamination)

2A

Table 2. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples after implementation of the CSTD and after cleaning (start test period)

3

Table 3. Cyclophosphamide (CP) and 5-fluorouracil (5FU) in wipe samples one year after implementation of the CSTD.

Materials and methods

Twelve locations were chosen to be tested for environmental contamination with the cytostatic drugs cyclophosphamide and 5-fluorouracil. The twelve locations included five within the pharmacy, five in the infusion suite area and two in office spaces. The areas tested remained identical throughout the study, with the exception of the automated drug distribution station which was replaced in the first quarter of 2011. Testing sites were determined, measured and the area of each was calculated in square centimeters.

The wipe samples were taken three times. The first samples were obtained on 25 June 2010, the second samples were obtained over the period between 18 and 27 August 2010, and the third samples were obtained on 19 August 2011. All samples were collected by the lead pharmacist at the cancer center. The first samples were collected in June 2010 without prior cleaning to measure the baseline levels of contamination that was occurring with use of the containment technique being used at the time. Implementation of the CSTD occurred concurrently in the pharmacy and the infusion suite in July 2010. Time was allotted for the pharmacy technicians and the nurses to adjust to using the new devices. The pharmacy, infusion suite and offices were cleaned using wipes that contained sodium hypochlorite 0.55% solution. The cleaning was done by a pharmacist and pharmacy technician. The second samples were collected in August 2010 after the implementation of the new devices and the sodium hypochlorite cleaning technique to determine whether the contamination was fully removed. The third samples were collected in August 2011, approximately 1 year after implementation of the devices.

The EquaShieldÕ system24 uses a double membrane for drug transfers to ensure dry connections. The unique syringe is airtight and contains two chambers, the distal chamber for air and the proximal for liquid. Likewise, the connector has two needles to allow for air and liquid exchange. The air contained behind the plunger of the syringe (distal) is transferred into the drug vial when liquid drug is withdrawn into the syringe (proximal).

The wipe samples were taken using Cyto Wipe Kits (Exposure Control Sweden AB). To collect test samples, an aliquot of 0.03 M sodium hydroxide solution from the Cyto Wipe Kits was applied to each target area and wiped off twice with dry tissue paper. The tissue paper was then placed in a plastic container with a screw cap and immediately frozen and stored.

The samples were analysed on a gas chromatography-tandem mass spectrometry method system. Specificity and sensitivity are increased using gas chromatography-tandem mass spectrometry method instead of gas chromatography/mass spectroscopy.25,26

The analysis of 5-fluorouracil was performed on a high-performance liquid chromatography system with ultraviolet detection.10,11

Results

Thirty-six samples were collected throughout the study. The results of the analysis of the wipe samples are presented in the Tables 1–3. The contamination per square centimeter is calculated assuming a 100% recovery and wipe efficiency. Thus, all results are underestimates. The detection limits for the analysis of cyclophosphamide and 5-fluorouracil were 0.10 and 5 ng/mL sodium hydroxide, respectively.

The results from the first two sets show contamination with cyclophosphamide on about half of the positions in all departments during both collection periods (Tables 1 and 2). However, levels of contamination were very low and mostly just above the detection limit of the analytical method. The highest level of contamination was found on the door and handle in the pharmacy. Contamination was found in one of the office spaces upon the second collection. Contamination with 5-fluorouracil was only observed on the dispensing counter in the pharmacy during the second collection period. The results from the final collection period show no contamination with cyclophosphamide or 5-fluorouracil in the pharmacy, infusion suite or offices of the cancer center. 

Discussion and conclusion

Exposure to antineoplastic agents is harmful to healthcare workers. Surfaces that are contaminated are touched when healthcare personnel are not using PPE. Sampling of the biological safety cabinet was not done in this study. The outside of vials being used during compounding may be contaminated with cytotoxic agents.27 Our goal was not to show that contamination exists inside the biological safety cabinet but rather to determine whether common areas were more likely to cause exposure, if contaminated, of healthcare personnel.

The initial sampling results showed environmental contamination with cyclophosphamide in several departments. However, the level of contamination was very low compared with historical data.12 Contamination with 5-fluorouracil was only observed at one position. This is probably caused by a higher detection limit for the analysis of 5-fluorouracil compared to cyclophosphamide.

Sodium hypochlorite-containing wipes were used to clean surfaces prior to the second sampling. This is not ideal, as bleach is not effective at removing all antineoplastic agents and the concentration of the wipes was low. However, this is the generally accepted cleaning practice at this institution. It was essential to determine that the CSTD would reduce surface contamination given the chosen cleaning process.

Other studies have shown environmental contamination with cytostatic drugs in pharmacies and administration areas.10–12 The initial results of this study showed very low levels of contamination with cyclophosphamide and 5-fluorouracil compared to the reference data.

The final sampling results, one year after the implementation of the closed-system transfer devices, showed an environment free of contamination from cyclophosphamide and 5-fluorouracil.

At our practice site, nurses must enter the pharmacy to retrieve prepared chemotherapy products for patient administration. The door and handle are touched repeatedly by all personnel, pharmacy and nursing, while not garbed in PPE. Finding the highest level of contamination on this surface was not surprising, but it was confirmation that PPE alone cannot protect healthcare workers from antineoplastic agent exposure.

One of the samples from an office was from a desk of a physician’s support nurse. The employee did not administer chemotherapy nor did the staff member work in the infusion suite. Finding contamination with cyclophosphamide at this location demonstrated that surface contamination could spread throughout a building.

The years of experience and expertise of the pharmacy technicians (a combined 21 years of experience for two technicians) at compounding antineoplastic agents may have been a reason for the low level of contamination initially. In addition, the expertise of the infusion suite nurses (each averaging twenty years of experience) likely contributed to this observed low level of contamination.

Implementation of the closed-system transfer devices for preparing and administering chemotherapy eliminated surface contamination with cytotoxic agents at the ambulatory cancer chemotherapy infusion center.

The NIOSH22 and United States Pharmacopeia’s current USP 79723 standards only recommend the use of CSTDs when preparing and administering chemotherapy. A ‘‘safe’’ level of exposure to antineoplastic agents by healthcare workers is unknown. Based on the positive findings that CSTDs can eliminate surface contamination with antineoplastic agents, guidelines should be adapted to require their use.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

The authors have no conflict of interest to disclose.