The handling of cytotoxic drug injections and compounding of parenteral nutrition solutions are both high-risk activities but pharmacists are in a strong position to implement safety measures and effective error-reduction strategies
Christine Clark
Freelance medical writer
The handling of cytotoxic drug injections and compounding of parenteral nutrition solutions are both high-risk activities but pharmacists are in a strong position to implement safety measures and effective error-reduction strategies
Christine Clark
Freelance medical writer
Opening the symposium, Laurence Goldberg (Independent pharmacy consultant, UK) said that mistakes are inevitable in complex work such as that undertaken in hospital pharmacies. Errors can harm not only patients but also health care staff who sometimes become ‘second victims’ when patients are harmed. Hospital pharmacists are in strong position to implement error reduction measures and two areas where this is particularly relevant are the preparation of cytotoxic drug injections and compounding of parental nutrition solutions.
Klaus Meier, President of the European Society for Oncology Pharmacy
Simbarashe Mavhunga, Advanced pharmacist, aseptic dispensing, NHS Tayside UK
Laurence Goldberg, Independent pharmacy consultant, UK
Chemical contamination
In recent years the workload for hospital pharmacists has increased but there has been no additional funding to help pharmacies cope with this pressure, according to Klaus Meier (President of the European Society for Oncology Pharmacy (ESOP). For example, there will be 23.6 million new cases of cancer worldwide by 2030 – 68% more than in 2012. There is also increasing use of antineoplastic drugs and in 2015 the National Institute for Occupational Safety and Health (NIOSH) added 34 drugs to its list of potentially hazardous agents. All of this increases the need for safety and efficiency in the pharmacy. There are not only risks to patients but also to staff – in fact, exposure to chemical or biological substances is one of the major workplace risks for healthcare personnel, he emphasised.
The unintended exposure of a healthcare professional to hazardous drugs is often described as ‘chemical contamination’. It can lead to acute effects such as skin disorders, allergic reactions and hair loss and chronic effects including adverse reproductive events and, possibly, cancer.
The management of safe handling procedures (MASHA) project (see Box) involves collecting wipe samples as a way of monitoring environmental contamination. In part I of the project, pharmacy personnel were trained in a standardised technique for wipe sampling. A PharmaMonitor kit, which contains all the necessary items for collection and dispatch of samples, was used.
Five different areas were sampled in each pharmacy. These were the work surface within the BSC or isolator and floor beneath the BSC or isolator, the checking counters in the clean room and in the store room and the refrigerator door. The samples were analysed for the presence of 12 drugs – cyclophosphamide, docetaxel, doxorubicin, etoposide, epirubicin, 5-fluorouracil, gemcitabine, ifosfamide, irinotecan, methotrexate, paclitaxel and topotecan using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The pharmacies had differing workloads ranging from 5000 to 80,000 preparations per year.
One of the findings was that the cleaning procedure was one of the most important factors relating to contamination. As a result, daily cleaning with 70% isopropyl alcohol or ethanol on a moist tissue was recommended after preparation in the pharmacy or administration on the ward. Once a week, a two-step cleaning procedure was recommended.
The first step involved cleaning using a cloth or tissue moistened with 0.05 M sodium hydroxide and the second step, 70% isopropyl alcohol or ethanol. A reference value of 0.1ng/cm2 was taken for all drugs (any value above this was recorded as being positive). The results showed that the proportion of positive samples (of 814) was 19% in part I, 15% in part II and 14% in part III.
A more detailed examination of the results showed that the overall levels of contamination also decreased. As expected, the most highly-contaminated areas were the work surfaces inside the BSC/isolator and the floor beneath the BSC/isolator.
An observational study was carried out in Heidekreis-Klinikum (Soltau, Lower Saxony, Germany) hospital pharmacy over 180 preparation days (from February to October 2016) when a closed system medical device portfolio (supplied by B Braun Melsungen) was used routinely. This pharmacy normally prepares 1500–1600 cytotoxic drug doses per year. The results showed that contamination with 5-fluorouracil (5FU) (the most frequently used product) and cyclophosphamide (the product that is most difficult to clean) was sharply reduced when using the closed system portfolio.
Mr Meier concluded that the closed system reduced the risk of contamination and the safety that it provided was affordable. However, there was one factor that was beyond the phamacy’s control and that was the contamination on the exterior surfaces of the drug vials, which can affect the processes and has to be considered as well.
Safe handling procedures for hazardous drugs can dramatically reduce the potential exposure of health care workers to these drugs; they should be implemented at all points where there is the potential for exposure of staff or patients. These include receipt and storage of drugs, drug preparation, administration, transportation, and waste handling, including patient waste, drug waste, and laundry.
In summary, Mr Meier said that the MASHA project has provided an overview of the cytotoxic contamination and the local procedures for safe handling of cytotoxic drugs in European hospitals. Evidence of contamination is still being found but the levels differ between hospitals. The study conducted in Heidekreis Klinikum has demonstrated that in order to reduce contamination, it is necessary to implement safe products which, when used together, provide closed system during reconstitution, transportation, administration and disposal.
In conclusion, the two key steps to decrease contamination of hazardous substances are appropriate implementation of cleaning procedures and appropriate choice of devices. The next steps will be to formulate safe handling procedures based on the European Society for Oncology Pharmacy (ESOP) Quality Standards for the Oncology Pharmacy Service (QuapoS). These will deal with the whole process from drug delivery to pharmacies through to their use in wards. A collaborative research programme with the European Society of Medical Oncologists (ESMO) and the European Society of Paediatric Oncology (SIOPE) is also planned. This will include 50 hospitals and be concerned exclusively with the handling of cytotoxic drugs on wards.
At present there is no quality management in this area and practices for preparation and administration of drugs are inconsistent, he explained. “We need to look for devices that can make this a safe procedure because it is important to protect health care staff from the risks of occupational exposure to cytotoxic drugs”, he concluded.
Parenteral nutrition
Parenteral nutrition (PN) solutions are high-risk products because of their complexity and the dangers posed if prepared or administered in error, Simbarashe Mavhunga (Advanced pharmacist, aseptic dispensing, NHS Tayside, UK) explained. Products containing visible precipitates can easily be identified and withdrawn but micro-crystallisation can also be hazardous and is difficult to detect, he continued.
PN is prescribed for patients of all ages with underlying health problems or who are unable to tolerate nutrient by the enteral route. PN has been defined as “the administration of nutrients (amino acids, glucose, +/- fat, electrolytes, trace elements and vitamins) by either a large central vein such as the superior vena cava or a peripheral vein in the arm”.
In the UK, licensed PN formulations, available in multi-chamber bags (MCBs), are routinely used. For example, 2-in-1 formulations contain standard mixtures of glucose and amino-acids and 3-in-1 formulations contain glucose, amino-acids and lipids. However, these standard bags do not always match patients’ needs and so further manipulations have to be performed in pharmacy aseptic units. When undertaking such procedures in an unlicensed aseptic compounding unit, the biggest challenge is ensuring that the final mixtures are supported by suitable physico-chemical compatibility and stability data. However, it is not always easy to find the relevant information – it is not included in the Summary of Product Characteristics, he said. Often, it falls to the compounding pharmacist to make a decision and take responsibility for the final product.
The PN compatibility software, EasyComp, which has been in use at NHS Tayside for more than six months, “makes the whole process straightforward”, said Mr Mavhunga. EasyComp is a validated compatibility database, providing a window of compatibility, which is based on about 12,000 laboratory tests. Before EasyComp became available, bespoke bags could not be made at weekends or over public holidays because it was not possible to contact manufacturers of PN solutions to confirm the stability of admixtures.
EasyComp
EasyComp allows the clinician to prescribe the nutrition formulation that is required. Stability is automatically verified in the pharmacy, and a worksheet can be generated and a label can be printed. The label includes all the information required for administration, including the contents and rate of administration, so that nurses know exactly what to do.
The compatibility data is stored on a central server whereas the patient data is stored on local (hospital) computers so the hospital retains complete control over confidential information, said Mr Mavhunga. Another benefit of the central server is that when the database is updated with new information it is immediately available to all users, he noted.
In NHS Tayside, some 2500 PN bags are compounded each year. The previous system relied on transcription of patient information from the prescription chart on to a PN order, then further transcription in the pharmacy from PN order to worksheet and into spreadsheet software to produce the label.
A study in 2004 by the American Society of Parenteral Nutrition showed that the transcription error rate in PN was 39% for prescribing and 24% for administration. “Given the number of transcriptions required in the previous Tayside system, the risk of error was quite high”, said Mr Mavhunga.
Now that EasyComp is in use, PN prescribed by the clinicians can be entered directly into EasyComp, and a worksheet and label are generated without any further transcription in the pharmacy. One important feature of EasyComp is that it provides instructions on the sequence of mixing of PN ingredients – “if you get it wrong there is a risk of precipitation and crystallisation”, emphasised Mr Mavhunga. In addition, EasyComp verifies that regimens are suitable for the intended patients. This makes the pharmacy quality assurance process more robust as pharmacists are able to confirm that a formulation is suitable for a given patient before it is compounded, he explained.
Mr Mavhunga presented a virtual tour of the EasyComp software to illustrate the way in which it is used in practice. The system is preloaded with all the available products, amino acids, lipids and MCBs from B Braun and additives from other manufacturers. The process is started by entering patient data (name, patient ID, weight, height, date of birth, etc). At this stage the system is not integrated with the hospital patient administration system and so the information has to be entered manually, he noted. Next the regimen is selected – either a standard product with or without modifications or the ingredients for a bespoke bag.
A ‘check compatibility’ button activates the checking procedure. If incompatibilities are detected, then a warning appears on a red background together with further information about how to adjust the regimen to make it stable. The problematic ingredients are also highlighted by a red background. If the suggestions are accepted, then the bag will be adapted accordingly at the click of a button.
A dose check is also available to verify that the regimen is in line with current dosage guidelines for the patient. The default shelf-lives for all formulations are seven days when refrigerated and two days at room temperature but can be shortened, if required locally.
The date of preparation and administration is by default today’s date, but it can be changed if necessary. This information will appear on the label and worksheet, explained Mr Mavhunga. Once all this is done, the worksheet, label and prescription sheet for the patient’s file can be printed.
Before implementation of EasyComp software an audit of 165 bags showed that there were 18 errors (56% were transcription errors, 5% were due to incorrect formulation calculation and the remainder were labelling errors). A post-implementation audit of 158 bags showed that there had been an 88% reduction in worksheet and label-generation errors – two errors occurred during the manual data input process, he acknowledged.
In addition, reducing the number of transcribing processes from four to one made for a faster turn round time and made the pharmacy workflow more efficient, he commented. Safe and secure archiving was another benefit, he added.
The satellite symposium, Risk prevention in hospital pharmacy was held during the EAHP Congress in March 2017. The symposium was sponsored by B Braun Melsungen AG
