More than 18,000 delegates attended the 43rd ASHP Midyear Clinical Meeting in Orlando, Florida, in December 2008. Key topics included aspects of medicines safety and hazardous drug handling
Laurence A Goldberg
Editorial Consultant HPE
At the opening ceremony of the meeting Jacqueline Surugue (president, European Association of Hospital Pharmacists, and chief pharmacist, Centre Hospitalier Georges Renon, Niort, France) received the Donald E Francke Medal for her leadership in advancing the pharmacy profession and serving professional organisations, including the International Pharmaceutical Federation (FIP). In her award lecture describing the impact of globalisation on pharmacy she pointed out that there is pressure for change from economists, investors and patients, who are now unwilling to accept differences in healthcare standards between countries.
The Treaty of Rome, which underpins the European Union, provides for the free movement of people, goods and services between its 27 Member States. Pharmacy education within the EU has been harmonised since 1985.
Many pharmaceutical companies have outsourced processes such as manufacturing and packaging. However, counterfeiting of medicines has been globalised, and this will be a major threat in the future, she predicted. Closer monitoring of medicines at all stages by pharmacists might be one way to tackle this, she suggested. The lack of worldwide standardised nomenclature for medicines is a barrier to free circulation at
present. A common coding system is useful for people but essential for data-sharing between computers – as in the food industry – she said.
Another global problem that must be tackled is pollution of the environment with pharmaceuticals. Cross-border mobility and the outsourcing of healthcare services will be among the most challenging problems of globalisation, she suggested.
At the recent global congress on the future ofhospital pharmacy (held in Basel, Switzerland, August 2008 – see report in HPE 41), there was a consensus amongst the 78 participant countries that they shared a similar vision for the future of hospital pharmacy. “Let us create throughout the world a culture of accountability … and write the gospel of hospital pharmacy for the benefit of patients,” Ms Surugue concluded.
Handling of hazardous drugs
In 2008, United States Pharmacopoeia (USP) chapter 797 was revised to include a section on the compounding of sterile doses of hazardous drugs. Luci Power (senior pharmacy consultant, Power Enterprises, San Francisco, USA) explained that the original version referred to the compounding of sterile products and made no reference to hazardous drugs. The revisions advocate containment of hazardous drugs by environmental and primary engineering controls (see Resources).
USP 797 is an enforceable standard that is used by regulatory agencies such as the Food and Drugs Administration (FDA), emphasised Ms Power. The revised USP 797 mandates specific primary engineering controls, such as class II biological safety cabinets (BSCs) and compounding aseptic containment isolators (CACIs), to contain contamination during reconstitution and transfer of hazardous drugs. The FDA favours preventive measures rather than the removal of contamination wherever possible, noted Ms Power. The revised USP 797 also specifies environmental controls for both compounding and storage of these drugs.
However, “The Class II BSC is only as good as the person who uses it. Poor training, poor work practices and a misunderstanding of the limitations of BSCs have led to continuing contamination in the work area and of the workers,” she said. Residues of hazardous drugs are found on compounded products either because there is contamination of the outer packs when they arrive from the manufacturer or because of leakage during the compounding process.
Decontamination – removal of hazardous drugs – can be a problem because the cleaning process itself can spread the hazardous drugs further. Surface decontamination of containers should always be carried out using wet cloths or wipes. “Spray the cloth and wipe the surface – only spraying the surface without wiping simply spreads the contaminant,” advised Ms Power.
Tom Connor (research biologist, NIOSH, Cincinnati, Ohio, USA) told the audience how the National Institute for Occupational Safety and Health (NIOSH; see Resources) recommends the use of closed-system drug transfer devices (CSTDs) to reduce contamination during drug compounding and administration.
Leakage of drugs during compounding occurs as a result of overpressurisation or poor technique, and this cannot be overemphasised, he said. Studies using fluorescein have shown that leakage of droplets is common when ordinary needles, syringes and connectors are used. Most hazardous drugs have low vapour pressures, but some, such as carmustine and nitrogen mustard, have relatively high vapour pressures and can vaporise readily. HEPA filters and 0.22 micron filters were designed to trap particles and do not contain vapours, he said.
The use of CSTDs will reduce environmental contamination.
They should be used as supplements to cabinets and isolators, and staff should be trained to ensure that they are able to use these devices correctly, said Dr Connor.
Asked how to determine which device protects staff best, Dr Connor recommended testing devices with fluorescein and requesting supporting evidence from manufacturers. He also noted that titanium tetrachloride, which forms white smoke on contact with moist air, has been used to check for air-tightness in CSTDs. NIOSH does not yet certify CSTDs in the same way as it does respirators, he added.
About 50% of medication errors occur at the point of
administration, and yet only 2% of errors are captured at this point. This represents a huge gap in safety, Stuart Levine (informatics specialist, Institute for Safe Medication Practices, Philadelphia, USA) told the audience at a satellite symposium organised by the Institute for Safe Medication Practices (ISMP).
Traditionally, the design of medicines’ labels has been largely based on pharmacy needs, but the needs of the end-user must also be considered. Nurses and others who administer medicines need the label to help them to match the medicines to the medication administration record (MAR). “The label should help the nurse to make the right decision,” said Dr Levine. The current practice of labelling with the product name and strength leads some people to assume that this is the dose. “Focus on the end-user,” advised Dr Levine. The minimum acceptable font size is 12 point – “It must be big enough to read – many nurses are over 45 years of age,” he said. Further details of safe formats for labels for other formulations are available on the ISMP website (see Resources).
Barcoding for intravenous (IV) drugs
The 2005 ASHP national survey showed that nearly 50% of hospitals did not have a formal quality improvement
programme for sterility and accuracy of intravenous admixtures. Karen Fiumara (medication safety officer, Brigham and Women’s Hospital, Boston, USA) explained how IV preparations could be tracked using barcoding.
In her hospital, IV doses prescribed in the computerised
physician order entry (CPOE) system are clinically approved and passed electronically to the sterile production room. From there onwards each step in the preparation process is tracked by barcode identification. If an incorrect product is scanned at any point a warning message appears. The system is similar to the tracking system used by FedEx in that all stages can be seen, explained Dr Fiumara. A more elaborate set of controls is built into the process for handling multiple dilutions, such as neonatal doses. For example, when a dose of 1.5mg hydrocortisone is needed, the only available product contains 100mg. When 2ml of diluent is added it makes a 50 mg/ml injection. In this case the system will generate four barcoded reconstitution labels to cover the four-stage process – reconstitution to give 50 mg/ml, dilution to 10mg/ml, dilution
to 1 mg/ml and drawing up of 1.5mg doses. Each step requires set-up, preparation and check processes to be completed. “This system cannot be bypassed – it will not let you cheat,” said Dr Fiumara. “We must implement quality assurance programmes to assess baseline risks – errors are occurring that we don’t know about,” she concluded.
Outsourcing IV compounding
The main reasons for outsourcing intravenous (IV)doses can be summarised as “standards, staffing andsafety”, said David Kvancz (chief pharmacy officer,Cleveland Clinic, Cleveland, Ohio, USA). A recentsurvey showed that hospitals with 300 beds or moreoutsource 70–80% of intravenous doses, whereas
smaller hospitals outsource a smaller proportion of their IV requirements.
At the 1,300-bed Cleveland Clinic the pharmacy dispenses one dose every four seconds and injectable medicines are now driving drug costs, explained Mr Kvancz. The pharmacy was built in the 1970s when the inpatient load was half and outpatient visits were one-sixth of current levels.
The required standards for preparation of sterile doses are set out in USP chapter 797. According to a 2008 survey, many US hospitals are unlikely to be able to comply with all the requirements for another two or three years. Moreover, obtaining budget approval for improvements is likely to be difficult in the current economic climate. Outsourcing enables managers to avoid appointing new staff and permits reallocation of existing staff to cope with other demands.
A major source of anxiety for pharmacy managers is the safe preparation of new products. “We get a new order and just make it,” said Mr Kvancz. There may be no validation of the preparation process at that stage, and the absence of a standard operating procedure (SOP) increases the risk of errors. Outsourcing companies are adept at handling product preparation research, SOPs and stability studies. In addition, routine quality assurance measures such as environmental controls, process controls and end-product testing are probably
not done in all hospitals.
Mr Kvancz reminded the audience that pharmacy managers are still responsible for the quality of the outsourced products that they purchase. He believes that outsourcing of IV drugs is most likely to be cost-neutral, rather than cost-saving. The main reason for this is that outsourcing companies will be carrying out much more quality assurance than most hospital pharmacies, he explained. Mr Kvancz concluded that the IV room is the next frontier for barcoding and robotic preparation.
Experience of working in an IV room had shown Miriam Klein (medication safety fellow, Kingsbrook Jewish Medical Center, New York, USA) that nurses often called for information about infusion rates and compatibilities because they did not have this information to hand at the time of administration. This was one of the factors that prompted her to design and test peelable labels for injectable medicines.
Reports in both the USA and the UK show that administration of injectable medicines is the step most commonly associated with errors. One example of this is the heparin overdoses that have been reported in both countries. Part of the problem is that most systems require healthcare professionals to write labels and apply them to the syringes. Often this is not done, but when it is done the information is sometimes abbreviated or is incorrect. Even a colour-coding system introduced in the UK by the Royal College of Anaesthetists went wrong and mix-ups occurred because the colours looked different to anaesthetists wearing laser surgery glasses.
Dr Klein has designed labels for ampoules and vials that incorporate reconstitution and dosing information as well as space to write dose, date and time of expiry and the initials of the operator. Surveys of pharmacists, nurses and anaesthetists have shown that the labels have been well received and are seen to be useful.
Tom Gray (chief pharmacist, Derby Hospitals NHS Foundation Trust, UK), who has worked with Dr Klein on this project, emphasised the importance of purchasing for safety. This means ensuring that products are fit for purpose. Labelling is a key element of this. Other recommendations that had emerged from the purchasing for safety initiative included standardisation of drug products and infusion devices, effective product labelling for selection and differentiation, and use of barcoding for accurate identification and reconciliation. Rapid access to essential information for products and the use of smart pumps were also considered to be important.
Institute for Safe Medication Practices (ISMP) – devoted entirely to medication error prevention and safe medication use. www.ismp.org
USP Chapter 797 USP 797 2008 Guidelines. http://www.usp797.org/ USP797-2008-Guidelines.htm
National Institute for Occupational Safety and Health www.cdc.gov/NIOSH