Understanding risk factors
Preparation of injectable medicines incurs patient-safety risks. The risk assessment tool identifies a number of product- and process- related risks which contribute to the overall risk of preparation. For additional information refer to the article Introduction to aseptic manipulation of injectable medicines (SPS page).
The outcome of the assessment will help pharmacy teams identify the most suitable location for preparation in their organisations and how risks can be managed and mitigated.
In some cases such as cytotoxic systemic anticancer chemotherapy (SACT) and parenteral nutrition (PN), it is not possible to mitigate the risks of preparation in clinical areas. In that case preparation in a pharmacy aseptic unit is mandated.
When defining governance for injectable medicines, organisations should consider the level of complexity and number of manipulations that can be safely undertaken in a clinical area.
Risk factors
The risk assessment tool considers several factors.
Therapeutic risk
Describes circumstances where there is significant clinical risk of patient harm if the injectable medicine is not prepared or administered as prescribed.
Therapeutic risk depends upon the inherent pharmacological properties of the medicine. It remains regardless of the dose, indication or route of injectable administration.
An indicative list (originally compiled at Oxford John Radcliffe Hospital), based on those medicines reported to the NPSA to have caused severe harm or death is given below. For further information see
(Safety in doses: medication safety incidents in the NHS. PSO/4, 2007) and Institute of Safe Medication Practice’s list of High-Alert Medications (2007)
These lists should not be relied upon as comprehensive or all-inclusive. They are a guide only and not a substitute for local professional judgement.
- Advanced Therapy Medicinal Products (ATMP)
- Anticoagulants and agents affecting the coagulation cascade
- Anticonvulsants with narrow therapeutic range, for example phenytoin
- Aminophylline
- Amphotericin, aciclovir, voriconazole
- Biological agents including monoclonal antibodies
- Cardiovascular active agents including sympathomimetics, beta-blockers, antiarrhythmics, dinoprostone
- Systemic Anti-Cancer Therapy (SACT)
- Hypertonic or hypotonic injections and infusions including glucose concentrations above 10%, including electrolyte concentrates such as Potassium chloride injection, magnesium sulfate 50% injection
- Insulin
- Investigational Medicinal Products
- Medicines used by spinal, epidural and intrathecal route
- Parenteral nutrition
- Neuromuscular blockers
- Opiates
- Oxytocin
- Sedative and anaesthetic agents
- Venoms, toxins and live vaccines
Further guidance on assessment of ATMP and gene therapy medicines can be found in the article Performing preparation risk assessments for ATMPs (SPS page).
High-risk route of administration
This includes those routes which present inherently enhanced risks which may be potentiated if doses are prepared and administered by clinicians unfamiliar with them. Routes include intra-ocular, intrathecal, intra cerebral, epidural and intra-osseous.
Use of a concentrate
Dilution of some medicines, such as concentrated electrolytes, is required before administration. Injection of the undiluted medicine may cause harm.
Complex calculation
This can be interpreted differently by different users. To encourage objectivity the “complexity” and error potential of the following situations should be carefully considered. The list is not exhaustive and each preparation should be assessed individually
Multiple preparation steps
Any calculation with more than one step for preparation. Examples include double or serial dilution.
Multiple calculation steps
Any dose calculation with more than one step such as:
- administration rates of microgram/kg/hour or nanogram/kg/hour or mg/hour or /day
- dose unit conversion required, for example mg to mmol or % to mg
- complex fractions or decimal places involved
- calculating a displacement value in adult practice
But excluding:
- calculation of displacement values in paediatrics (where it is routine practice)
- weight-based calculations where the calculation is part of the prescription
Complex method
This can be interpreted differently by different users. Each preparation should be assessed individually. To encourage objectivity, consider the “complexity” and error potential of situations such as the following:
- more than five non-touch aseptic manipulations involved
- syringe-to-syringe transfer
- preparation of a burette
- any “open system” manipulations such as use of ampoules
- mandatory removal of fluid from infusion container
- preparation does not follow SmPC recommendations exactly
- multiple preparations needed to administer a single “dose” because the shelf-life of the infusion is shorter than 24 hours, or less than the expected duration of infusion
Reconstitution of powder
Where a dry powder has to be reconstituted with a liquid.
Use of part or multiple vials or ampoules
Measuring and drawing up the contents of a part container or multiple containers is more complex. It is also more error‑prone than drawing up the whole contents of a single vial or ampoule.
Use of an infusion device
All infusion devices require some element of calculation and set up which therefore has potential for error and should be considered as a risk factor. However, it is important to note the benefits of using an appropriate rate control device usually exceed any added risks.
Ambulatory infusion devices
Use of an ambulatory elastomeric infusion device is considered high-risk. Prolonged exposure to near-body temperatures increases the risk of microbial proliferation after accidental contamination.
Use of a non-standard administration set or device
The most significant patient-safety risk associated with less-commonly used devices is that they may not be immediately available or that clinicians are not familiar with their use. Examples include:
- light protective
- low-adsorption administration sets
- non-standard in-line filters
- air-inlets for rigid infusion containers
- injection pen devices