Preventing exposure to cytotoxic drugs

An important new initiative designed to protect healthcare professionals working across the EU has been launched^.1 Why is it needed?

Cytotoxic drugs describe a group of medicines designed to destroy cells that grow in a rapid and uncontrolled manner, preventing their replication or growth. Cytotoxic drugs are generally non-selective, meaning that they do not differentiate between malignant cells and normal healthy tissue and are therefore likely to damage normal (non-tumour) cells, resulting in adverse health effects.²

Cytotoxic drugs are increasingly being used in a variety of healthcare settings, prominently in the treatment of cancer but also to treat non-cancerous diseases such as multiple sclerosis and psoriasis. In addition, the number of preparations and administrations of cytotoxic and other hazardous drugs is continuously growing because of the demographic development and expanded therapeutic potential.³

It is well documented that healthcare workers who handle cytotoxic drugs are at potential risk from exposure when control measures are inadequate. Scientific studies have shown that the risk of exposure in the working environment is commonplace despite safety policy improvements, and even with recommended precautions in place.

In particular, nurses, pharmacists and pharmacy technicians have the greatest risk of potential exposure.⁴ In addition to health professionals, personnel involved in cleaning, transport, laundry and waste disposal of hazardous drugs or contaminated material, are also at risk.

Healthcare workers may be exposed to these hazardous drugs by inhalation of contaminated air or by skin contact with contaminated surfaces, clothing and medical equipment which is the most problematic route.

The health hazard for medical personnel handling these drugs is a major concern as they are not only classified as potentially carcinogenic, but also mutagenic or toxic to reproduction.³ Because cytotoxic drugs are highly effective active substances, exposure to even negligible concentrations of certain drugs may be hazardous for workers who handle them or work near them, especially if daily exposure continues over many years.^3,5

Since it was first recognised that occupational exposure to cytotoxic drugs posed a potential health risk to exposed workers, various groups, institutions and agencies around the world have developed and published different guidelines or recommendations for the safe handling of these agents.

On the basis of the existing regulations, guidelines, standards and recommendations, the International Society of Oncology Pharmacy Practitioners (ISOPP) produced international guidelines in 2007 under the title ‘ISOPP Standards of Practice Safe Handling of Cytotoxics’, covering all possible items related to the safe handling of cytotoxic medicines.⁶

The ISOPP standard recommends that precautions in a hierarchical order of prevention (similar to the Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work)⁷ (see Table 1).

European and national regulations, relating to carcinogens, mutagens or substances toxic to reproduction, stipulate the identification of the exposure of workers and regular checks of the effectiveness of the technical protective measures taken by the employer.^7–9 For both tasks, either workplace measurements or other methods to identify the exposure of workers are mentioned. In addition, ‘Directive 2004/37/EC on the protection of workers from the risks related to exposure to carcinogens or mutagens at work’ stipulates the measurement of carcinogenic substances for early detection of abnormal exposures resulting from unforeseeable events or accidents.⁷

However, while Directive 2004/37/EC sets occupational exposure limits (OELs), only a few are currently available. Moreover, these OELs are only applicable to environmental air concentrations and not for surface contamination or skin contact. Given that there is more contamination from cytotoxic drugs on surfaces than in the air and that measurement of surface contamination is currently the only indication of the amount of environmental contamination in areas where hazardous drugs are prepared, administered to patients or handled, it can be concluded that OELs are therefore not suitable for monitoring current working conditions in the healthcare sector.

At a national level, guidelines and recommendations for the safe handling of cytotoxic drugs have been issued and implemented by some Member States to minimise the risk of occupational exposure. However, because there are no harmonised standards of practice or guidelines, significant differences persist with regard to handling of cytotoxic drugs.

The European picture shows that, while some Member States have adopted the standards of the ISOPP (such as Belgium and Spain) or higher, standards in other countries do not reach the same level of protection or are non-existent. In some countries, such as Germany or The Netherlands, guidelines have been provided by scientists or national associations, but not necessarily supported by the respective Governments.

Studies have demonstrated that despite significant improvements in the safe handling of cytotoxic drugs over the plast 20 years and implementation and issue of various guidelines and recommendations, contamination of the working environment and exposure of healthcare workers still continues. This leads to the conclusion that additional steps must be taken at the national level to ensure the protection of healthcare workers.

Engineering controls used to remove hazards or place a barrier between the worker and the hazards demonstrate a reduction in environmental contamination and exposure to workers. However, as the engineering controls are designed for prevention of microbiological contamination, chemical contamination may still occur. Examples of engineering controls include the use of biosafety cabinets, isolators and safety-engineered medical devices.

Appropriate personal protective equipment (PPE) (lowest position in the hierarchy of protection measures of the ISOPP standards) – protective gloves, gowns, eye protection, facial protection, respiratory protection apparatus, cap, shoe covers, etc – is used by all healthcare workers who may come into contact with cytotoxic agents. Moreover, it is critical that healthcare workers are educated in the appropriate selection and use of PPE for protection against exposure to cytotoxic drugs. Nevertheless, while the use of personal protective equipment represent an important protection tool, they need to be preceded by other measures such as engineering controls and administrative controls because their protective capacity is only temporary and partial.

Closed-system drug transfer devices (CSDTs) (second position in the hierarchy of protection measures of the ISOPP standards), that is, those devices that mechanically prohibit the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system, are the only devices that have been specifically designed to protect healthcare workers from occupational exposure to hazardous substances. CSDTs have been successful in significantly reducing surface contamination and/or the amount of these agents in the urine of exposed healthcare workers.^10,11

The use of CSDTs has been widely recommended by different existing guidelines, standards or recommendations, such as the National Institute for Occupational Safety and Health (NIOSH) alert on Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings’.⁵

In its guide for safe handling of cytotoxic drugs, the International Society of Oncology Pharmacy Practitioners (ISOPP) states that CSTDs are the best, most effective, preventive measure to avoid exposure to contamination during cytotoxics preparation and administration.

Administrative controls includes policies and procedures and staff education and training.

Healthcare workers may be unaware of the risks of working with cytotoxic drugs and the necessary precautions. In order to understand the risks involved and to ensure the safe handling of these agents, all staff involved in the handling of cytotoxic drugs must be provided with suitable, sufficient and up to date information and education on on a regular basis. This requires that all personnel involved in the preparation and administration of cytotoxic drugs have a recognised qualification or have received certified training relevant to their work. In addition, regular assessment of practice should be undertaken of all personnel preparing and administering chemotherapy, in order to verify compliance with procedures.

In order to minimise the risk of chronic occupational exposure of cytotoxic drugs, decontamination, cleaning and disinfection of work surfaces where cytotoxic drugs are handled or potentially contaminated, is critical in reducing the spread of contamination. Unfortunately, no single chemical can completely clean, disinfect and decontaminate surfaces contaminated with cytotoxic drugs and even with techniques employed to clean contaminated surfaces, is still difficult to reduce the residual concentration of cytotoxic drugs found on work surfaces below the limit of detection.

Despite efforts, contamination of the workplace (safety cabinets and isolators, work tops, floors, vials, equipment, etc) with cytotoxic drugs still occurs, and workers remain at risk of exposure. Hence, it is crucial to investigate the release and spread of the drugs to help identify possible sources and routes of exposure, as well as to control and improve the effectiveness of protective measures and equipment.

This can be achieved through an effective monitoring programme for the collection of reliable exposure data. However, as occurs with the handling practices of cytotoxic drugs, chemical contamination monitoring varies across Member States, with some Member States having poor or non-existent monitoring programmes or guidelines. It is important to stress that, under the current EU legislation, employers are obliged to offer employees a monitoring programme for carcinogenic compounds – this includes most cytotoxic drugs.

Monitoring should become a standard in all the Member States and performed on a regular basis. A regular repetition of monitoring has proven to have a stronger effect on the reduction of contamination levels and workers’ exposure than incidental monitoring.

While the risk posed by cytotoxic drugs is recognised by the European Agency for Safety and Health at Work and publications from the Directorate-General for Employment, Social Affairs, as well as through national guidelines in Member States, there is currently no harmonised approach to the prevention of this chemical risk in the healthcare sector properly reflected in European legislation.^3,12

In spite of a lack of harmonisation, safer, healthier working conditions remains key to improving job satisfaction and a healthier workforce across Member States. Implementing this clear commission initiative would start to address the long-term effects of these working environments on an ageing demographic. This is in line with the Europe 2020 strategy objectives for smart, sustainable and inclusive growth.¹³

Eventually, this could help to ensure a better retention of the healthcare workforce in a context where most EU countries report difficulties in retaining and recruiting health staff with increasing shortages predicted in the longer term.^14–18 The impact of having healthier work environments is significant as the healthcare sector constitutes one of the most significant sectors in the EU economy, whose demand will increase dramatically with Europe‘s ageing population.¹⁶

In light of these considerations, it is imperative to appreciate the dangers of these hazardous medications, to adhere to the safety mechanisms, and to use the available safety resources in order to avoid the potential risks associated with working with these agents. Continuous education of healthcare providers is fundamental to ensuring safety and positive outcomes. Safe handling procedures can be implemented by adhering to appropriate standards and consistently integrating them into policies.

The EU must commit to a new era of safe handling of hazardous medicines by specifically addressing in its legislation the issue of healthcare workers’ exposure to hazardous drugs and chemicals, in particular during the preparation and administration of cytotoxic drugs. This must be addressed by harmonising national provisions relating to the protection of workers by measures to prevent exposure or to keep exposure at a level as low as possible.

• Exposure to cytotoxic drugs over the course of employment poses a danger to health and is potentially mutagenic, carcinogenic and toxic to reproduction.
• Scientific studies show that risk of exposure in the work place is commonplace despite safety policy improvements and precautions being in place.
• The occupation exposure limits set out by EU and national guidelines lack suitability as they are only applicable to environmental air concentrations and not the more problematic surface and skin contamination.
• Engineering controls in place to protect workers from hazards are designed for prevention of microbiological contamination; therefore chemical contamination may still occur.
• Regular monitoring of exposure, rather than incidental monitoring is proven to be more effective in reducing contamination levels and worker exposure.

 

References

1. European Parliament. www.europarl.europa.eu/sides/getDoc.do?pubRef=-//EP//TEXT+REPORT+A8-2015-0312+0+DOC+XML+V0//EN (accessed October 2016).
2. National Institute for Occupational Safety and Health (NIOSH). NIOSH list of antineoplastic and other hazardous drugs in health-care settings 2014. US Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2014-138 (supersedes 2012-150).
3. European Commission Directorate-General for Employment, Social Affairs. Occupational health and safety risks in the healthcare sector – Guide to prevention and good practice;2011.
4. Centers for Disease Control and Prevention. Occupational exposure to antineoplastic agents.www.cdc.gov/niosh/topics/antineoplastic/ (accessed October 2016).
5. National Institute for Occupational Safety and Health. 2004 NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in health care settings.www.cdc.gov/niosh/docs/2004-165/pdfs/2004-165.pdf (accessed October 2016).
6. International Society of Oncology Pharmacy Practitioners. 2007 ISOPP Standards of Practice. Safe Handling of Cytotoxics. www.oncosystems.com.tr/dosyalar/_ISOPP_Standards_of_Practice_-_Safe_Handling_of_Cytotoxics.pdf (accessed October 2016).
7. Directive 2004/37/EC of the European Parliament and the Council of 29 April 2004 on the protection of workers from the risks related to exposure to carcinogens or mutagens at work (Sixth individual Directive within the meaning of Article 16(1) of Council Directive 89/391/EEC).
8. Council Directive 98/24/EC of 7 April 1998 on the protection of the health and safety of workers from the risks related to chemical agents at work (fourteenth individual Directive within the meaning of Article 16(1) of Directive 89/391/EEC).
9. Hazardous Substances Ordinance (Gefahrstoffverordnung – GefStoffV) of 26 November 2010 (BGBl. I p. 1643). www.baua.de/en/Topics-from-A-to-Z/Hazardous-Substances/TRGS/pdf/Hazardous-Substances-Ordinance.pdf?_blob=publicationFile (accessed October 2016).
10. Sessink PJM et al. Reduction in surface contamination with antineoplastic drugs in 22 hospital pharmacies in the US following implementation of a closed-system drug transfer device. J Oncol Pharm Pract 2011;17:39–48.
11. Sessink PJM, Trahan J, Coyne JW. Reduction in surface contamination with cyclophosphamide in 30 US hospital pharmacies following implementation of a closed-system drug transfer device. Hospital Pharmacy 2013;48(3):204–12.
12. European Agency for Health and Safety at Work. Current and emerging issues in the healthcare sector, including home and community care European Risk Observatory Report. https://osha.europa.eu/en/publications/reports/cur-rent-and-emerging-occupational-safety-and-health-osh-issues-in-the-healthcare-sector-including-home-and-community-care/view (accessed October 2016).
13. European Commission. Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions on an EU Strategic Framework on Health and Safety at Work 2014-2020COM(2014) 332 final. http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2014:332:FIN (accessed October 2016).
14. European Commission, Directorate-General for Health and Food Safety. Recruitment and retention of the health workforce in Europe; 2015.
15. European Commission. Green Paper on the European Workforce for Health (COM/2008/0725 final); 2008.
16. European Commission. 2012. Commission Staff Working Document on an Action Plan for the EU Health Workforce. 6 October 2014.
17. European Commission. 2012. Commission feasibility study on EU level collaboration on forecasting health workforce needs, workforce planning and health workforce trends.
18. European Centre for the Development of Vocational Training 2012. Skills demand and supply forecasts.