Use of injectable medicines for multiple doses

Understanding risks

Manipulation of injectable medicines is associated with a risk of contamination and error. These risks are explored in detail in the article about aseptic manipulation of injectable medicines (SPS page). Another article provides advice on assessing risks when reconstituting injectable medicines (SPS page).

Use of injectable medicines for multiple doses increases the likelihood of contamination because the container is entered more than once, and subsequent storage increases the risk of microbial proliferation. It also introduces the potential for medication errors and mix-ups associated with part-used vials and unlabelled syringes.

Clinical areas and patient homes naturally contain large numbers of microorganisms so accidental contamination may occur, even when using aseptic non-touch technique.

Where multiple use is unavoidable, robust risk assessment, governance oversight, and risk mitigation measures are essential.

This article aims to inform professional judgement in clinical practice. 

Licensing of multi-dose and single use medicines

Some medicines are licensed for multiple use and usually contain a preservative to inhibit microbial growth. Typically, these are licensed for the intramuscular or sub-cutaneous route.

Most injectable medicines do not contain a preservative and are designed for single and immediate use. Use of single use injectable medicines for multiple doses is ‘off label’, so liability rests with the organisation.

For medicines licensed for multiple use, this may not be stated on the label, but will be evident from Section 6 (Pharmaceutical Particulars) of the SmPC.

Medicines with no SmPC, for example UK manufactured Specials, should all be assumed to be for single use.

Single use of single use containers

This is the most appropriate and the safest clinical practice, and reduces risks to patients if doses are administered immediately after preparation.

For medicines presented in a ready-to-administer form, for example a pre-filled syringe or infusion bag, ‘single use’ means that the dose is used for one patient on one occasion.

For medicines requiring aseptic manipulation before administration, ‘single use’ means a single withdrawal is made from the original sealed, sterile container. This is usually into a syringe immediately before administration to the patient or addition to an infusion container, in accordance with the SmPC.

Ampoules, bags and pre-filled syringes are all single use containers. Vials may be licensed as multi-dose containers as the closure is a resealable bung.

Multiple use of licensed multi-dose containers

Some medicines are licensed for multiple use. In most cases these are intended for one patient, for example pre-filled pens are licensed for multiple use but must never be shared between patients. Some multi-dose vials may be suitable for use for multiple patients, for example some vaccines.

Preservatives

Most multi-dose medicines contain preservatives and are supplied in vials for sub-cutaneous or intramuscular administration.

Pharmaceutical preservatives are active against a wide range of microorganisms, including bacteria, yeasts, and fungi. Their presence significantly reduces the risk of microbial proliferation if the product is contaminated during use.

Preservatives can be toxic or irritant at high concentrations and may be sensitising to some patients. They may be unsuitable for use by some routes of administration, or for certain patient groups. This means that they are avoided in most injectable medicines.

Where preservatives are used, they are added only in low concentrations to minimise these negative effects. However, this also means they are only effective against low bioburden challenges and do not cover all types of micro-organisms. Preservatives cannot ‘re-sterilise’ the injectable medicine once its container has been contaminated.

Use for more than one patient

Containers shared between patients can act as a vector in the transmission of infection because preservative systems are not perfect.

If contamination and microbial proliferation were to occur, use for multiple patients would mean multiple patients could be harmed.

An organisational risk assessment should be undertaken to determine whether multi-dose vials should be restricted to one patient or may be shared between patients. The risk assessment should consider the following factors.

Likelihood of contamination

The likelihood of contamination increases

• when microorganisms are present in large numbers, for example, in ward areas and patients’ homes
• the more times a single container is used
• if there is poor compliance with aseptic non-touch technique

Likelihood of microbial proliferation

Following contamination, the likelihood of microbial proliferation increases

• during a long in-use shelf life
• during storage at non-refrigerated temperatures
• if the multi-dose vial is unpreserved

Consequence to patient

If the medicine is contaminated, the consequence to patients will be more severe

• if the patient or patient group is particularly vulnerable to infection, for example older adults, neonatal patients, and immunocompromised patients
• if the medicine is administered by a high-risk route, for example spinal or intravenous

Example

Insulin is presented in multi-dose preserved vials.

Hospital X permits the use of insulin vials for multiple patients to support

• out-of-hours treatment of patients requiring immediate doses in acute inpatient areas
• ward level preparation of insulin infusions

A local risk assessment concluded that the benefits of timely treatment outweighed the likelihood of infection in the patient cohort. Guidance on temporary insulin substitution on admission and a standard operating procedure on insulin infusion preparation were developed to support these practices.

Hospital Y uses insulin vials for one patient only. Their out of hours use is infrequent and the ward configuration permits storage of sufficient vials to meet several patients’ needs. Their patient cohort includes transplant patients who are more at risk from infection. The local risk assessment concluded that timely access could be achieved without the use of vials for more than one patient.

Multiple use of single use containers

Injectable medicines that are not licensed for multiple doses should only be used for one dose for one patient. This is stated in the National Patient’s Safety Agency’s NPSA(20) Promoting safer use of injectable medicines, published in 2007 and available in the government’s National Archives.

In exceptional circumstances, national shortages of specific critical medicines that cannot be prepared in a pharmacy aseptic unit may mean that temporary use for more than one dose is unavoidable. The practice should not become routine due to the elevated risks to patient safety and should be under continuous review.

In such a case, local organisational governance committees should consider a risk assessment covering all relevant factors and must consider whether risk mitigation measures will be effective in preventing patient harm. Risks include:

Likelihood of contamination

As identified above, the care setting, techniques used, the container type, and the number of times the container is used determine the likelihood of contamination occurring.

Once medicines in glass or plastic ampoules are opened, they are especially easily contaminated because they are open to the environment. These must not be stored following opening.

Likelihood of microbial proliferation

Following contamination, microbial proliferation will occur during storage because preservatives are not present to inhibit growth. The longer the medicine is stored after first use, and the higher the storage temperatures, the faster the microorganisms will proliferate.

The shortest possible in-use expiry time must be assigned and refrigeration used to slow microbial growth. Typically, this would not exceed 1 to 2 hours.

Risk of error

Single use medicines are not designed to be used more than once so there is no space on the label for recording an in-use expiry time. Even if an in-use expiry time is assigned, there is a risk the time will be exceeded due to unclear labelling.

If medicines are withdrawn into syringes for short term storage, for example if the original container was an ampoule, the identity and expiry time must be made clear.

Chemical stability

Medicines are formulated and packaged to prevent degradation. Some medicines are very sensitive to degradation which can occur as soon as the container has been opened or manipulated. The rate of degradation is dependent on time and temperature and therefore injections should be used as soon as possible after opening to minimise this risk.

If medicines are withdrawn into syringes for short term storage, for example if the original container was an ampoule, steps must be taken to ensure compatibility with the syringe during storage.

Consequence to patient

Use of single use medicines for multiple doses may result in the administration of a contaminated medicine to a patient. Administration via a high-risk route, or to a patient who is vulnerable to infection, may have catastrophic consequences.

Governance

Medicines policies should include the organisational position on use of injectable medicines for multiple doses and should describe arrangements for risk assessment and decision-making. The policy should draw a distinction between the processes for assessing multi-dose containers and single use containers.

Risk assessments should be undertaken by someone with the skills and knowledge to do so. The assessments must consider both infection risks to the patient and legal risks to the organisation associated with the use of medicines outside the terms of their Marketing Authorisations.

All decisions must be formally accepted by the organisation. Systems must be in place to monitor and review the safety of practices with injectable medicines.

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