Vaccinations remain one of modern medicine's greatest success stories. They are a safe and highly effective way to save lives by preventing a wide range of life-threatening and debilitating diseases, including measles, meningitis, polio and cervical cancer. However, the processes of storing, handling, and administrating vaccines are complex and require careful planning to avoid errors. Over a 3-year period from 2009 to 2011, 3.7% (153/4301) of enquires to the Vaccine Advice for Clinicians Services (Lang et al, 2014), concerned vaccine errors. This figure only includes errors related to administration and is therefore likely to be an underrepresentation of the true number of vaccine-related errors (Lang et al, 2014). PHE have recently updated national guidance on responding to vaccine incidents, including important details about breaches in the cold chain and recommendations for revaccination (Public Health England [PHE], 2019a).
Cold chain
Vaccines, like all biological substances, degrade over time. Exposure to extremes of heat, cold, sunlight or fluorescent light can accelerate this process. Recommended temperature ranges are detailed in the Summary of Product Characteristics (SPC) for each vaccine; however, as a general principle, vaccines should be stored between +2°C to +8°C in medically validated fridges and transported only in validated cool boxes (PHE, 2013; PHE, 2019a).
The ‘cold chain’ is a term used to describe the specific temperature conditions in which vaccines should be kept at from the point of manufacture to the point of use. Breaches in the cold chain may result in compromise to vaccine potency and this could lead to patients receiving inadequate immunisation. Figure 1 illustrates the expected cold chain that should be followed to maintain vaccine quality and efficacy.
Figure 1. A typical cold chain system for vaccines.
Cost of waste
Vaccines are an expensive and valuable resource. This has focused attention on vaccine wastage. During 2018, vaccine wastage reported through ImmForm (a web-based system used to record vaccine uptake and vaccine ordering facilities for the NHS) had a list price value of around £6.3 million—73% of this cost was thought to be related to avoidable incidents (PHE, 2019b). Figure 2 highlights that many of these avoidable wastage incidents were related to refrigeration and, therefore, breaches in the cold chain.
Figure 2. Causes of avoidable vaccine wastage reported through ImmForm 1 January 2018 – 31 December 2018.
Guidelines and policies
Local policies should be in place to ensure that vaccines are stored, handled, and administered correctly, and that vaccine incidents are appropriately managed. Local policies should reflect national policy and best practice recommendations which are summarised in Box 2. The guidelines on how to respond to vaccine incidents have been recently updated and now include specific information about temperature deviations and revaccination, as well as a template letter for those requiring revaccination (PHE, 2019a).
Box 1.Are you reporting vaccine wastage on ImmForm?Any vaccines ordered via ImmForm that have not been used should be recorded using the ImmForm Stock Incident web form. The Stock Incident reporting tab is found on the Vaccine Supply homepage.
Box 2.Resources for good practice
- Public Health England (PHE) ‘Protocol for ordering, storing and handling vaccines’ guidance (PHE, 2014)
- PHE ‘Responding to errors in vaccine storage, handling and administration’ guidance (PHE, 2019a)
- PHE. Immunisation against infectious diseases: storage, distribution and disposal of vaccines. The Green Book Chapter 3. (PHE, 2013)
- Order your copy of the ‘Keep your vaccines healthy’ poster (code CCPVP01) and fridge magnet (code CCPVM02) from www.healthpublications.gov.uk
Breach in the cold chain
Exposing vaccines to any temperature outside the manufacturer's recommended range is considered a breach of the cold chain. The significance of the breach is dependent on the length of time spent outside of the recommended cold chain conditions, the temperatures to which the vaccines were exposed to, and the stability of certain vaccines. Further information about vaccine stability is available from:
- Vaccine manufacturers—increasingly, SPCs for some vaccines will contain information on vaccine stability outside the normal +2°C to +8°C temperature range
- WHO Temperature Sensitivity of Vaccines. Available at: http://apps.who.int/iris/handle/10665/69387
- PATH. Summary of stability data for licensed vaccines. Available at: www.path.org/resources/summary-of-vaccine-stability-data/
Generally, vaccines available for use in the UK are very stable and able to withstand short temperature excursions outside the recommended temperature range. ‘One-off’ fluctuations in fridge temperatures rising above +8°C but lasting less than 20 minutes, such as may occur when stock taking or restocking, are therefore unlikely to affect vaccine stability and potency (PHE, 2019a).
Exposure to high temperatures
Exposing vaccines to higher than recommended temperatures accelerates the natural decline in potency. This acceleration is more apparent at very high temperatures (>37°C) than for prolonged storage at moderate temperatures (+15°C to +25°C) (PHE, 2019a). For example, the half-life of the Gardasil HPV vaccine is estimated to be 130 months at temperatures up to +25°C, reducing to 18 months at +37°C and 3 months at 42°C (Shank-Retzlaff et al, 2006).
Exposure to low temperatures
A vaccine's sensitivity to freezing temperatures is dependent on the vaccine's preparation. Liquid formulations for example diphtheria, tetanus, acellular pertussis (DTaP) and rotavirus vaccine are more freeze-sensitive than freeze-dried preparations such as measles, mumps and rubella (MMR) and varicella (PHE, 2019a). Vaccine vials that are exposed to very low temperatures may develop microscopic cracks due to volume expansion of liquids on freezing. Bacterial contamination can occur via these cracks and can increase the risk of local reaction or systemic infection (World Health Organization, 2006; PHE, 2013). Any vaccine that has been frozen or known to have been subjected to temperatures below 0°C should be disposed of.
Top tips for good practice
- Place orders every 2–4 weeks, according to need
- Store vaccines promptly in a medically validated fridge after delivery and until point of use
- Keep vaccines in their original packaging
- Rotate stock to ensure vaccines with shortest expiry date are used first: ‘first in, first out’
- Use validated cool boxes to store vaccines if carried elsewhere, and label any unused vaccines before returning them to the fridge so that they can be easily identified and used at the next possible opportunity
- Ensure all members of the care team understand the importance of good vaccine management. This includes reception staff, as often they will be the first to receive delivery of vaccines.
Responding to cold-chain breach
Despite all reasonable precautions being in place, breaches of the cold chain can still occur. It is necessary to act on each breach immediately. Specialist advice should be sought—for example from the local NHS Screening and Immunisation Team—and an informed assessment made as to whether the vaccine has been compromised. If the vaccine has been compromised then appropriate actions must be taken to safeguard patients, minimise wastage and maintain public confidence in vaccination programmes. The process is summarised in Figure 3.
Figure 3. Summary of actions for responding to a cold chain breach adapted from PHE recommendations, see guidance for full details
Responding to errors
Expired vaccines
Expired vaccines should not be administered to patients as their potency is likely to have declined over time. Where a vaccine has been given outside of its expiry date, the vaccine will usually need to be repeated. Regular stock control, rotation and using the ‘first in, first out’ method ensures that short expiry-date vaccines are used first. In some exceptional circumstances, such as during times of extreme vaccine shortages, PHE may release expiry extension recommendations. However, in general, vaccines should only be used within their expiry date (PHE, 2016).
Errors with diluents and reconstitution
Some vaccines require reconstitution with specific diluents such as stabilising agents or buffers (to achieve the correct pH before administration). Therefore, using the wrong diluent could potentially destroy the vaccine or reduce its potency. For some vaccine preparations, the diluent contains another vaccine antigen (eg Infanrix hexa or Menveo ACWY conjugate vaccine), and so failure to reconstitute the vaccine correctly could mean that not all the required antigens are given to the patient. When an administered vaccine has been found to be incorrectly reconstituted, or mixed with the wrong diluent, it will usually need to be repeated (PHE, 2019a).
Errors with dose
Vaccines administered to patients that are greater than the recommended dose will not usually affect the overall immune response or protection afforded by the vaccine. They may, however, result in an increased risk of an adverse reaction. Where vaccines are administered to patients at less than the recommended dose (eg if some vaccine spills or leaks out as the vaccine is being administered), the vaccine will usually need to be repeated, as the dose the patient received may not be sufficient to evoke a full immune response (PHE, 2019a).
Errors with vaccine schedule
While generally not harmful, vaccines administered sooner than the recommended age may not induce a good immune response or provide the desired boosting effect for long-term protection. In some instances, these vaccines may need to be repeated when the individual reaches the recommended age (PHE, 2019a).
Errors with dosing interval
Vaccines given sooner or later than the recommended dosing interval may lead to a reduced immune response and revaccination may be required. Specific intervals are detailed in the Green book and can vary between vaccines. Live attenuated and inactivated vaccines with the same antigens should usually be administered at an interval of less than 4 weeks. Where vaccines have been given at less than the recommended interval, the dose should be repeated once the recommended time interval has elapsed from the vaccine given too soon and usually at least 4 weeks from the last dose given. Patients should be advised that additional doses may lead to an increased risk of local reactions but are required to ensure an adequate immune response. Specific intervals must also be observed when administering two or more different live attenuated vaccines. For example, yellow fever and MMR vaccines should be given 4 weeks apart as the co-administration of these two vaccines could lead to a suboptimal immunisation against yellow fever, mumps and rubella. Practice nurses are advised to check guidelines detailed in Chapter 11 of the Green book, particularly when administering more than one live vaccine (PHE, 2020).
Defective vaccines
Prior to administration, vaccines should be inspected visually for any foreign matter and/or abnormal physical appearance. All defective vaccines should be discarded and reported to the MHRA via the Yellow Card Scheme or via email to dmrc@mhra.gsi.gov.uk. Where one has been inadvertently administered, revaccination should be considered.
Box 3.Vaccine diluentsMost diluents are less sensitive to storage temperature than vaccines; however, manufacturers' advice should be followed. Prior to reconstitution of a vaccine, diluents should be at the same temperature as the vaccine to avoid thermal shock to the vaccine. ‘Thermal shock’ is damage to a vaccine that can occur when a diluent that is at too high a temperature (above +8°C) is added to a vaccine. Vaccines should be stored in their original packaging keeping the vaccine and the diluent together.
Box 4.Protect your vaccines, protect your patientsRegular review of cold chain storage conditions should be standard practice following the four ‘R’ steps:READ: take a daily reading of the thermometer's maximum, minimum and current temperatures at the same time every day during the working weekRECORD: record temperatures in a standard fashion, on a standard form and sign each entry on the recording sheetRESET: reset the thermometer after each reading. The thermometers should also be reset when temperatures have stabilized after periods of high activity, eg restockingREACT: the person making the recording should take action if the temperature falls outside the +2°C to +8°C range and document this action
Box 5.Case studyTwo practice nurses new to immunisations, Conor and Lina, are running a clinic in the afternoon with several patients booked in for flu vaccinations. In anticipation of a busy clinic, and to avoid multiple trips to the fridge, which is in the treatment room down the corridor from the clinic, Lina suggests keeping the vaccines in their clinic room for easy access.Conor checks the SPC for the vaccines. This recommends storing the vaccines in their original packaging in a medically validated fridge at between 2°C and 8°C. It is not clear how long the vaccines can be outside the fridge without compromising the potency of the vaccine.Lina checks the Green Book and the Public Health England (PHE) vaccine incident guidance which states that most vaccines used in the UK are relatively stable and can tolerate temperatures above +8°C for up to 20 minutes.Conor remembers that they have a lunch box that they used for their annual summer barbecue, and wonders whether they could use those to store the vaccines in their rooms. They ask Tori, a district nurse who regularly takes vaccines out for home visits, for some advice. Tori refers them to PHE guidance for storage and handling of vaccines and explains that the advice on vaccines being stable for up to 20 minutes has been included as reassurance in case of a short breach—such as may occur when stock-taking/re-stocking—rather than permission to store vaccines outside of the recommended +2–8°C range. Tori reports that district nurses use a validated medical grade cool box and cool packs to transport vaccines on home visits. She explains that district nurses take only enough vaccines for patients that they expect to immunise and label any unused vaccines before returning them to the fridge for use at the next possible opportunity.Conor and Lina recognise that it is important to maintain the cold chain, and that only validated cool boxes are suitable for this. They decide to keep the flu vaccines in the fridge and collect one as and when required for each patient. While this can be difficult to do in a busy clinic; they agree that it is best practice in order to protect vaccines and protect patients.
Responding to vaccine incidents and revaccination
Where a vaccine incident has been identified, and a compromised vaccine has been administered to a patient, the priority is to assess the risk to the patient and ensure that good practices are in place to avoid any reoccurrence. Recipients of compromised vaccines may not mount an adequate immune response, and may, therefore, not receive the desired long-term protection afforded by the vaccine. An initial investigation should help to decide whether the vaccine incident was sufficient to warrant informing patients of the error under the duty of candour guidelines and whether the incident may have adversely affected the potency of the vaccine(s) such that revaccination would be recommended under the duty of care.
Revaccination is usually safe, but there are some associated risks, including increased vaccine reactions, and loss of public confidence in service providers and immunisation programmes. Therefore, the decision to revaccinate patients should be based on a thorough risk assessment that balances the public health risk of receiving a sub-potent vaccine against any potential risks from revaccination.
The Green Book and PHE vaccine incident guidance should be reviewed when considering revaccination (PHE, 2019a; PHE, 2020). As well as a template letter to patients, the guidance includes information about factors that need to be considered in assessing the need to revaccinate, such as the type of vaccine, whether it is a one-off repeated dose or part of a multiple-dose schedule and whether it is a booster or primary vaccine. Table 1 summaries the risks associated with revaccination and special considerations for different types of vaccines detailed in the PHE vaccine incident guidance (PHE, 2019a).
Table 1. Summary of risk associated with revaccination following receipt of a compromised vaccine and special considerations for different vaccine types
Vaccine type | Risk associated with revaccination | Special considerations and relevant information |
---|---|---|
Live vaccines | No additional risk of adverse events from giving additional doses of most live vaccine | BCG - Repeat vaccination is not usually recommended. High risk of local reaction and keloid scarring |
Inactivated vaccines | Frequency of local or systemic reactions with certain inactivated vaccines may increase with additional doses given | Acellular pertussis (aP) local reactions are more common in children receiving their fourth dose of aP |
Combination vaccines | Local reactions are more common with additional doses of some combination vaccines like DTaP-containing vaccine. Please see the Green book for PHE guidance for further details | Required antigen is often not available as a single dose. Risk of revaccination with combination vaccine is preferable to the consequences of no protection |
Routine schedule doses | For most routine scheduled vaccines, there is no additional risk of adverse events from giving additional doses. However, special consideration is required for combination vaccines as highlighted above | Repeat dose of vaccine should be given in addition to routine scheduled doses. Ensure a minimum interval before revaccination dose |
Duty of candour and patient consent
When a vaccine-related incident occurs, those involved need to decide whether patients should be informed under the duty of candour. Requirements to notify may vary depending on specific circumstances; however, the Nursing and Midwifery Council (NMC) have issued joint guidance with the General Medical Council (GMC) on the professional duty of candour (NMC and GMC, 2015). In line with this guidance, recipients of compromised vaccines must be informed that they may not be protected by the vaccine(s) that they have received. Recipients should be informed of the incident, receive an apology, and offered remedial actions where appropriate (such as revaccination). The PHE incident guidance includes a template letter to patients and carers who are offered revaccination (PHE, 2019a).
Conclusion
Safe and effective vaccination is reliant on strict adherence to protocols for the storage, handling and administration of vaccines. When errors occur, an informed decision needs to be made as to whether the vaccine has been compromised and if so, whether it presents a risk to patients. The updated national PHE guidance sets out how to do this and outlines the corrective actions that should be taken in response to vaccine incidents (2019a). Effective management of vaccine incidents is crucial in minimising waste and in ensuring patient safety.
KEY POINTS:
- Vaccination is one of the most successful and cost-effective public health interventions
- Safe vaccine administration depends on maintenance of the cold chain throughout transportation and storage, and right to the point of administration
- Most vaccines used in the UK can tolerate ‘one-off’ cold chain excursions of above 8°C for up to 20 minutes. For longer breaches, seek expert advice
- Vaccines given too early, without sufficient spacing or, in rare cases, too late may need to be repeated
- Decision to revaccinate patients should be based on a risk assessment
- Vaccine-related incidents must be recorded and appropriately investigated to avoid repeat incidents and ensure patients are protected
CPD reflective practice:
- What is your practice protocol in the event of a breach in the cold chain?
- Where can you get further information on vaccine management and storage?
- Where can you get information about revaccination?
Further reading and useful information
- The e-Learning for Healthcare Immunisation programme (https://www.e-lfh.org.uk/programmes/immunisation/) consists of seven knowledge sessions which cover the core areas of immunisation that healthcare practitioners need to be familiar with in order to deliver immunisations safely and effectively. This includes one session on vaccine storage and one on administration
- The Green Book. Chapter 3 includes detailed information about vaccine storage that is regularly updated
- The Electronic Medicines Compendium contains vaccine SPCs and vaccine manufacturer details (last section of SPC). www.medicines.org.uk/emc/
- Joint GMC and NMC guidance—Openness and honesty when things go wrong: the professional duty of candour. www.nmc.org.uk/standards/guidance/the-professional-duty-of-candour/
- The Royal College of Nursing ‘Managing Childhood Immunisation Clinics’ guidance provides brief practical advice on the recommendations outlined by PHE. https://www.rcn.org.uk/professional-development/publications/pub-007201