Risk evaluation for aseptic preparation

Risks to patients are greater when injectable medicines are prepared in clinical areas, such as wards and operating theatres, than when they are prepared in pharmacy. Risks of medication errors and microbiological contamination have been well documented.(1,2) However, instances of harm to patients from injectable medicines continue to be reported.(3)

In the UK, standards for aseptic preparation in pharmacy are strictly applied. The Medicines and Healthcare products Regulatory Agency (MHRA) require full EU GMP4 unless the National Health Service (NHS) complies with the five conditions outlined in Table 1.

The defined NHS guidelines(5) pre-date the PIC/S standards for preparation of medicinal products in healthcare establishments,(6) but are very similar with respect to aseptic products. The NHS aseptic standards are implemented throughout the UK by a regular programme of quality audits.(7)

Ideally, all injectable medicines should be prepared in pharmacy under these defined and inspected standards, and presented to nurses in a ready-to-administer form. Unfortunately, however, aseptic capacity within pharmacy is limited and the pharmaceutical industry has been slow to develop ready-to-use or ready-to-administer formulations. Consequently, nurses continue to prepare the majority of injectable medicines.(8) This same research showed that environmental standards and preparation practices in ward areas are very variable. Risks of medication errors and microbiological contamination were identified.

To make best use of the available capacity within pharmacy aseptic units, risk evaluation is a way of prioritising those products with higher risk for preparation by pharmacy. A risk assessment tool was developed(9) to identify high-risk products being prepared in clinical areas and to help the targeted transfer of these products to pharmacy. This tool became the basis of a Patient Safety Alert(10) in the UK on the safety of injectable medicines. This required risk assessment of practices and individual injectable products prepared in all clinical areas.

The risk assessment allows ranking of products with the aim of reducing risks by providing them in ready-to-use form or by giving guidance to reduce risks of preparation in clinical areas, such as by the provision of dose calculation tools, or step-by-step preparation methods (Table 2).

The risk factors for assessment of preparation in clinical areas in NPSA2010 are shown in Table 2.  Risk factors are assigned and totalled to identify high-risk products.

High (greater than six risk factors) or moderate risk products (three to five risk factors) should be targeted for transfer to pharmacy preparation. If this is not practical, for example for products with a short expiry period, other risk reduction measures should be introduced to improve patient safety. For example, introduction of dose calculation tools may help nurses avoid medication errors.

Lower risk products (one to three risk factors) can be retained and made in clinical areas with suitable training and the availability of sufficient technical information to allow the products to be made safely. Before injectable medicines are placed onto procurement contracts in the UK, they are subject to a quality assessment process. This includes an assessment of the availability and suitability of the technical information about the product (for example, suitable diluents, dilution instructions) to facilitate preparation. Also, in some Member States, national injectable medicine guides are available for use in clinical areas, which also reduces risk to patients.

Nurses preparing products of lower risk should be supported by pharmacy involvement in their training and given advice on ‘non-touch’ techniques. Publications in nursing journals(9,11) have highlighted the role that pharmacy can play and raised awareness of risks to patients from preparation techniques, for example.

Junior doctors may also be required to prepare injectable medicines, sometimes in an emergency situation. In Newcastle, training days have required junior doctors to pass a broth transfer test that simulates preparation of an injectable medicine, and also to pass a calculation test.

The UK Department of Health has produced a list of serious preventable patient safety incidents that should not occur, known as ‘Never Events’. Number four on this list relates to preparation of high-risk injectable medicines. It states that patients should not come to severe harm as a result of wrongly prepared high-risk injectable medicines. It requires hospitals to have their own lists of high-risk medicines, as identified by the NPSA risk assessment tool. This is the current situation in the UK.

A survey on quality assurance standards for preparation was carried out across the EU. The results(12) showed a wide variation between countries in standards for pharmacy preparation and a gap in standards between pharmacy and ward preparation.

This survey led to the Council of Europe Resolution.(13) Reconstitution is given a separate section in the Resolution and is defined as ‘a manipulation of a product with a marketing authorisation in line with its Summary of Product Characteristics.’

The Resolution requires reconstitution to be subject to a risk assessment. It goes on to state that high-risk products should be prepared in pharmacy but low-risk products can be prepared on wards. It also states that the healthcare establishment should decide where products should be reconstituted and that national authorities should develop legislation with the relevant professional bodies in relation to reconstitution.

This risk assessment for reconstitution mentions risk factors that are very similar to those identified in earlier publications:(8–10) complexity of process, the environment, the nature of the product, whether it’s an open or closed system, and the relevant education and training of staff involved.

The Resolution aims to harmonise quality and safety standards, and reconstitution is one of the workstreams. There is currently a European Directorate for the Quality of Medicines and healthcare (EDQM) working party on reconstitution. The working party has representatives from hospital pharmacists and regulators from different EU countries and is producing a guidance document on reconstitution that will help countries implement this part of the Resolution.

In summary, ideally all injectable medicines would be prepared in pharmacy; however, there is not sufficient capacity for this, so risks must be evaluated to allow targeted transfer of the higher-risk products. Lower-risk products can be prepared in clinical areas with risk reduction measures. The EDQM guidance document on reconstitution will help EU Member States to implement this part of the Resolution.