The European Commission Guidance for the safe management of hazardous medicinal products at work provides comprehensive instructions on how to handle hazardous medicinal products from identification to administration and even including laundry and wastewater management. In this series of short videos Paul Sessink – a member of the core team of authors – and Birgit Sessink – an experienced hospital pharmacist responsible for hazardous drug compounding at the University Hospitals of Leuven offer their insights into what the guidance tells us and how it works in practice.

Click to view the full guidance document

Hazardous medicinal products (HMPs) are defined as those which are carcinogenic, mutagenic or reprotoxic. Some three-four million people are working with these drugs on a daily basis and there is growing concern that this could have adverse long-term health effects for them. The guidance document is detailed but it is only necessary for users to refer to the sections of the guidance that are relevant for their jobs.

The majority of hazardous drugs can be found in standard lists such as the NIOSH (National Institute for Occupational Safety and Health) list of hazardous drugs in healthcare settings and the  European Trade Union Institute’s (2022) list of hazardous medicinal products.

What the EC guidance tells us about handling hazardous medicinal products

The European Commission guidance is not a law, although parts of the guidance are legal requirements in Europe, explains Dr Sessink.   A good example of this is the obligation for an employer to provide information and training to employees who have to handle hazardous drugs in the course of their work.

The key steps in managing hazardous drugs are

• Identification of hazardous medicinal products
• Risk assessment of hazardous medicinal products
• Monitoring of exposure
• Repeat the above steps whenever necessary to stay up-to-date

Employees who handle hazardous drugs should receive appropriate training and this should be regularly updated or refreshed to ensure that personnel are up-to-date with new products and devices and have not developed bad habits.

How much contamination is too much in the workplace?

Working with hazardous medicinal products (HMPs) calls for safe systems of working to minimise the risks of occupational exposure for staff. However, monitoring of contamination must also be undertaken to check that systems are working,

The most common risk for healthcare personnel is absorption of HMPs via the skin after contact with contaminated surfaces. Contamination with HMPs is measured by surface wipe testing and the results scan be interpreted using a ‘traffic lights’ model:

Measures to prevent contamination in the first place include the use of closed system transfer devices (CSTDs) and drug vials that have no exterior contamination when they arrive from the manufacturer. Staff who work with HMPs are protected by means of engineering controls, such as biohazard safety cabinets and CSTDs, to ensure that they do not come into contact with the drugs. In addition they wear personal protective equipment (PPE) comprising gowns, gloves etc.

How to make the EC guidance work in practice

At University Hospitals, Leuven the process for managing hazardous drugs from prescription to disposal is carefully controlled. At every stage, well-planned procedures minimise the risks of occupational exposure for the staff involved,

Compounded preparations are labelled in a distinctive way using labels with a yellow background and and additional ‘yellow hand’ label as a warning sign that it contains a hazardous drug.

Before they leave the pharmacy, compounded preparations are sealed in plastic over-wraps so that if there is a burst or breakage the drug is contained in the overwrap and does not contaminate a wider area.

Case study – responding to a large hazardous spillage

Even in the best systems things occasionally go wrong. Sometimes a whole series of events coincides and a serious incident occurs.  Ms Tans describes how one such event occurred in December 2023.

A prescription was received for cisplatin 190 mg in 1000ml of 0.9% sodium chloride. When the injection was prepared the assistant forgot to remove 200 ml of fluid before adding the cisplatin, so the bag was over-filled, with a final volume of 1200ml instead of 1000 ml. The pharmacist released the bag after discussion with the doctor who confirmed that the extra volume was acceptable as people receiving cisplatin require extra fluids anyway.  The infusion bag was covered with a yellow bag to protect the drug from light and then put into the protective over-package. However, the light-protecting bag was sealed together with the over-package and, in fact, the over-package bag was not sealed correctly or completely.

The preparation was required urgently on the ward and so a nurse came from the ward to collect it and carry it back to the ward. Under normal circumstances it would have been placed in a sealed box for transport to the ward.  When the nurse reached the corridor outside the pharmacy the preparation fell out of the unsealed bag and burst, resulting in spillage of 1200 ml cisplatin solution.  The nurse told the pharmacy department what had happened and then hurried back to the ward – with wet (contaminated) shoes – to take a shower and change her clothing.  Pharmacy personnel took a spill kit to clean up the spillage. Because of the large volume of the spillage, additional spill kits had to be obtained.  The spillage had occurred just before lunchtime in a busy corridor that leads to the staff restaurant so the task of preventing people from walking over the area and potentially spreading the drug further, was made more difficult. The cleaning department was asked to clean the whole area and the safety department was informed. It took almost two hours before the whole area was decontaminated, said Ms Tan.

As a result of this incident, some procedures were reviewed and refreshed and steps were taken to ensure that all staff were aware of the correct procedures to be followed.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.

“We’re working with people and people can do something wrong. So, all the procedures are there but sometimes somebody forgets something”, explains Ms Tans. Sometimes a whole series of events coincides and a serious incident occurs.  Ms Tans describes how one such event occurred at University Hospitals, Leuven in December 2023.

A prescription was received for cisplatin 190 mg in 1000ml of 0.9% sodium chloride. When the injection was prepared the assistant forgot to remove 200 ml of fluid before adding the cisplatin, so the bag was over-filled, with a final volume of 1200ml instead of 1000 ml. The pharmacist released the bag after discussion with the doctor who confirmed that the extra volume was acceptable as people receiving cisplatin require extra fluids anyway.  The infusion bag was covered with a yellow bag to protect the drug from light and then put into the protective over-package. However, the light-protecting bag was sealed together with the over-package and, in fact, the over-package bag was not sealed correctly or completely.

The preparation was required urgently on the ward and so a nurse came from the ward to collect it and carry it back to the ward. Under normal circumstances it would have been placed in a sealed box for transport to the ward.  When the nurse reached the corridor outside the pharmacy the preparation fell out of the unsealed bag and burst, resulting in spillage of 1200 ml cisplatin solution.  The nurse told the pharmacy department what had happened and then hurried back to the ward – with wet (contaminated) shoes – to take a shower and change her clothing.  Pharmacy personnel took a spill kit to clean up the spillage. Because of the large volume of the spillage, additional spill kits had to be obtained.  The spillage had occurred just before lunchtime in a busy corridor that leads to the staff restaurant so the task of preventing people from walking over the area and potentially spreading the drug further, was made more difficult. The cleaning department was asked to clean the whole area and the safety department was informed. It took almost two hours before the whole area was decontaminated, said Ms Tan.

“We learned a lot of out of this case”, she says. After the incident, some procedures were reviewed and refreshed and steps were taken to ensure that all staff were aware of the correct procedures to be followed.

Closing messages

“I would recommend people to take the European guidance document, which is unfortunately only available now in English but it will be translated to all member states’ …. languages. … I would recommend [that] people read that document and go to the table which is relevant for your profession, so you need not to read the whole document but just take the sections that are relevant, which are mostly three four five sections out of the whole document”, says Dr Sessink.  Readers should compare the recommendations with what is done in their own hospitals and consider whether improvements could be made. He emphasises the value of before and after monitoring of exposure to see if changes make a difference.

Ms Tans emphasises the value of training and education of personnel who work with hazardous drugs “so that people know what they’re doing”. They should have the right materials and the right procedures and training should be repeated and refreshed to ensure that people are up-to-date with new devices and materials. Finally, she says, “in case of a spill, stay calm”.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.

Prescriptions are received electronically in the pharmacy and are validated. They are then printed and a label is printed at the same time, to avoid transcription errors later. All the ingredients required are assembled and passed to the staff in the clean room. Only one preparation is made at a time. The preparation is made in the biohazard safety cabinet and before it leaves the clean room it is packed in a sealed bag. It is “put in an over-package which is a plastic bag and that’s sealed so if something should happen during transport, like for instance a bag that breaks, then the  … fluid that comes out of the bag stays in the outer package – so nothing comes out and we avoid spillage throughout the transport system”, explains Ms Tans.

A pharmacist carries out the final check of the compounded preparation – checking that it has been prepared correctly with the right products and the right dose. In addition to the medication label, “we also put a label with a yellow hand, which is a warning sign that it’s a hazardous drug”, she says.

All labels for hazardous drugs have yellow backgrounds, in contrast to the normal white labels, she adds. The labels are barcoded so each preparation can be followed throughout its journey. The barcode can also be scanned when the drug is administered to the patient.

The compounded preparations are then delivered to the wards either via the hospital’s pneumatic tube system or via the transport system, packed in closed, leak-proof boxes.

There are also procedures for cleaning of the cabinets after drugs have been prepared and procedures for dealing with accidental spillages of hazardous drugs, says Ms Tans.

Tips for success

Ms Tans and Dr Sessink offered a number of practical tips for success:

1. Choose vials in preference to ampoules because ampoules can cut the operator when opened and there is a risk of having glass particles in the final preparation
2. Choose sleeved vials if possible, then if they are dropped and the vial breaks, the contents are contained by the sleeve
3. Use Luer-locking syringes instead of Luer-slip syringes to reduce the risk of accidental disconnection and leakage
4. When preparing a hazardous drug in an infusion bag, first spike the bag and fill the administration line with saline or glucose solution from the bag. After that, add the drug into the bag. This ensures that if there is any leakage of fluid when the nurse connects the infusion to the patient, it contains only saline or glucose but not the hazardous drug – and the risk of contamination is avoided.
5. After a preparation has been made, put all the waste material into a plastic bag and seal it before putting it into the hazardous waste bin. This minimises the risk of environmental contamination with hazardous drug aerosols.
6. Never [dismantle] a system that has been used to prepare or administer hazardous drugs. If it can be kept closed, as far as possible, then the risk to waste management and cleaning staff is minimised.
7. Use closed system transfer devices.
8. Training and education make people continuously aware of the potential risk of exposure to hazardous drugs.
9. Meet other people and learn from them, for example, by attending local and international conferences.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.

Healthcare workers can be exposed to hazardous medicinal products (HMPs) via two main routes – inhalation, when powders are handled, or absorption via the skin, usually after contact with contaminated surfaces.  The second of these is the more common route and this is the reason why protective gloves are required.

When working with HMPs, “everything you can touch can be contaminated ….. so that’s the reason why you have always to wear … protective gloves …  because when it’s on your hands it can get into your body”, explains Dr Sessink.

Contamination with HMPs is measured by surface wipe sampling. This technique involves swabbing a defined area with a suitable liquid (e.g. using the wipe kit from Exposure Control) to collect the drug residues. After analysis the amount of drug in the swab can then be expressed as nanograms per square centimetre (ng/cm²).

The results can be interpreted using a ‘traffic lights’ model. “It gives you a first impression about the contamination and your working conditions. If it’s all low or ‘not detectable’, you have a good working procedure, all is fine. When it’s high, then there are probably spills and leakage and, …. according to the results you can make changes in your process or in the devices you are using”, he says.

Safe systems

One of the main reasons for having safe systems of working is to prevent contamination of the working environment with hazardous drugs and thereby prevent exposure of healthcare workers. Failure to prevent contamination in the first place just creates a lot of extra work in removing contamination, explained Dr Sessink. His own work, using wipe tests inside isolators and biohazard safety cabinets, has shown that HMPs are often present, indicating that spillages and leaks have occurred. “The point is, as long as it stays inside and is not getting out on a product, like an infusion bag or a syringe or whatever, then it’s fine – but there is never a guarantee that [a product] is clean when it’s leaving the pharmacy and going to nursing [areas]”, he says.  The way to avoid this problem is to use closed system transfer devices (CSTDs) for the preparation process. “If you have that process closed and there is no spill or leakage, you will not have a contaminated product and you will not spread the contamination – so I would say 90-95% of the problem can be solved there”, says Dr Sessink. The other source of contamination is drug vials that are contaminated on the outside when they arrive from the manufacturer. Dr Sessink’s advice is to specify that vials must be free of exterior contamination when they are purchased. “If you cover that clean vial issue and you cover the potential leakage by using CSTDs, almost the whole issue of contamination, aside from accidents, because they can always happen. Aside from accidents, the normal process can be 100% controlled”, he says.

Birgit Tans describes the measures that make up the safe systems of working at the Pharmacy Department in the Leuven University Hospitals. The people involved in compounding of HMPS wear gowns, gloves and other personal protective equipment (PPE) and work in BSCs (biohazard safety cabinets to ensure that they do not come into contact with the drugs. In addition, CSTDs are used to prevent the release of drug aerosols when drugs are transferred from vials to infusion bags. Because the devices are needle-free, needle-stick injuries are also avoided. The work is carried out following standard operating procedures and regular education and training is provided for the staff, she emphasises.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.

Click to view the full guidance document

The first point to make about the document is that “it guides you through the issue of potential exposure to hazardous drugs. It’s not a law …. but parts of the guidance are already law within Europe” explains Dr Sessink.   A good example of this is the obligation for an employer to provide information and training to employees who have to handle hazardous drugs in the course of their work.

Many of the recommendations are based on ‘good practice’ in the member states. Readers could use these to check their own practice standards, he suggests.

The guidance extends beyond pharmacy; when hazardous drugs are administered “there is a lot of exposure – we know it from testing, from all kind of studies done, that actually the nurses are the biggest group that are exposed to hazardous drugs”, says Dr Sessink. “There are good examples [of] how you can improve working conditions and safety for nurses within the guidance document”, he adds.

Employers are obliged to carry out a both risk assessments and exposure assessments when hazardous drugs are used.

The guidance document also covers other areas including veterinary use of hazardous drugs and cleaning and waste management.

Key steps

The key steps in managing hazardous drugs are

• Identification of hazardous medicinal products
• Risk assessment of hazardous medicinal products
• Monitoring of exposure
• Repeat the above steps whenever necessary to stay up-to-date

It is the responsibility of the employer to take these steps, usually with help from suitably-qualified specialists, says Dr Sessink

Training for handling of hazardous medicinal products

Healthcare workers who need to handle hazardous medicinal products require additional training, beyond their basic training as, for example, pharmacists or pharmacy technicians. Furthermore, it is important that such training is regularly updated or refreshed to ensure that personnel are up-to-date with new products and devices and have not developed bad habits. “It should be a continuous process to make people …..  continuously aware about the potential risk of being exposed”, says Dr Sessink. Once again, it is the employer’s responsibility to ensure that this happens and such training should be funded by the employer and should take place during working hours and not the employee’s free time, he emphasises.  This is a legal requirement “so it’s nothing new, but it’s practically mostly not done”, he adds.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.

Click to view the full guidance document

Hazardous medicinal products (HMPs) are defined as those which are carcinogenic, mutagenic or reprotoxic. Many countries have guidelines for handling such products but there is considerable variation between member states. Some three-four million people are working with these drugs on a daily basis and there is growing concern that this could have adverse long-term health effects for them. Moreover, many people working in the field said that there was a need for Europe-wide guidance. The final document is long and covers all aspects of HMP-handling, but it is organised in such a way that it is only necessary to refer to the sections of the guidance that are relevant for your job. “For instance, [if] you are a pharmacist, you have to read maybe four or five sections of the whole guidance which are relevant for you”, explains Dr Sessink.

Clearly, the first step is identification of HMPs.  There are a number of standard lists of hazardous drugs, for example the NIOSH (National Institute for Occupational Safety and Health) list of hazardous drugs in healthcare settings and the  European Trade Union Institute’s (2022) list of hazardous medicinal products.  However, there are also drugs that do not appear in the lists, for example, investigational drugs that are used in clinical trials. In such cases the producer of the drug should provide the necessary information, he says.

About Birgit Tans and Paul Sessink

Birgit Tans is a hospital pharmacist at the University Hospitals of Leuven in Belgium. For the past 30 years she has specialised in compounding of cytotoxic drugs and is an expert on safe handling of hazardous drugs.

Paul Sessink first studied chemistry and later completed a PhD on hazardous drug exposure. In 1995 he founded the company, Exposure Control to provide services related to monitoring of hazardous drugs in the working environment. The company has provided services to about 350 hospitals in the world.

Read and watch the full series on our website or on YouTube.