Guidance

Off-label vaccines: an introductory guide for healthcare professionals - text version

Updated 13 March 2023

Applies to England

Before they can be placed on the market, all medicines, including vaccines, have to have a license that allows them to be sold for use in humans. Sometimes, however, it is necessary to offer a vaccine that is ‘off-label’. This means that, although the vaccine is authorised for use, it’s being used in a way that is slightly different from the strict terms laid down in its license. This guide describes the circumstances that can lead to vaccines being used ‘off-label’ and the reasons why this may be recommended.

License for medical use

Having a licence means that the vaccine has been approved for use in certain people to protect against certain diseases and that the manufacturer can advertise or promote the use of the product for this purpose. The license reflects only the specific situations in which the vaccine was studied before the company submitted data to the licensing agency. So, for instance, a license may specify use in babies, but not older children, or it may specify use in adults but not in children. Or it may stipulate that 2 doses should be given 2 months apart instead of 3 doses one month apart.

This does not necessarily mean there is any suggestion that use in different situations is unsafe or ineffective, it just reflects the fact that trials need to have very strict criteria to ensure that the results are valid. It is often not feasible to study vaccines in every single population group or at every possible schedule before the vaccine is given its license. It would not be ethical to delay granting a license whilst every possible scenario was studied because many people would then be denied the benefits of preventing an infection now.

How a vaccine gets a licence

All vaccines have to be authorised by the UK Medicines and Healthcare products Regulatory Agency (MHRA), or the equivalent agency for Europe – the European Medicines Agency (EMA), before they can be placed on the UK market and advertised or promoted for use by the manufacturer. Vaccines are only submitted for licensing to the EMA or MHRA after they have been trialled in the target audience included in the license, which could be children or adults, and fully tested to ensure that they are:

• acceptably safe

• able to provide protection against the disease they are designed to protect against

• manufactured to a high standard of quality

This extensive testing process – from the first batch of a vaccine being made in a laboratory to its use in the general population – can take more than 10 years. The detailed information on the results of testing in the laboratory and from clinical trials is then submitted for independent evaluation by the experts at the MHRA or EMA.

Only when these agencies are entirely happy with this information will the company be granted a license to place the product on the market and to advertise or promote its use.

Amongst other things, the license specifies who can receive the vaccine, how many doses are required, what side effects may occur and how the vaccine should be handled and stored

Use of vaccines in ways not specified in the license

A medicine or vaccine can only be marketed and promoted for use by the license holder in accordance with the specifications of the license.

However, it is common in clinical practice for health professionals to prescribe a medicine for use in a different way from that stated in its license. This is because the health professional has additional information about the medicine or has exercised their professional judgement and decided that the medicine would still be appropriate for an individual patient. This is often referred to as ‘off-label’ use. The responsibility for such use rests with the health professional.

‘Off-label’ use of medicines is fairly common, particularly in children, as most medicines are tested first in adults and conducting studies in large numbers of children can be difficult. Many vaccines are designed to be used in children and have been tested in this age group, and so ‘off-label’ use of vaccines is much less common but does occur from time to time. Vaccine use is usually based on the recommendation of the Joint Committee on Immunisation and Vaccination (JCVI) – a UK committee made up of many independent experts on all aspects of vaccination.

Reasons patients may be offered ‘off-label’ vaccines

All routine vaccines currently used in the UK are licensed to be placed on the market. So, as well as having the data to support their safety and efficacy in accordance with the license, it means they have been manufactured to a high standard and have undergone independent batch testing before release. Sometimes, however, clinical experts on the JCVI recommend that the vaccine should be used in people who were not included in the initial trials or recommend that the number or timing of the doses is different from that used in the trials. As these situations were not specified in the license this would mean the vaccine was being used ‘off-label’.

This recommendation is normally based on additional evidence presented to the committee that may have been obtained by a research group independent from the manufacturer. Sometimes it reflects the expert clinical judgement of the members based on their understanding of how vaccines work in different patient groups. When a vaccine is being used ‘off-label’, it means that experts have advised that there are clear benefits of using the vaccine in this way and that the vaccine is still considered to be safe and effective. ‘Off-label’ use of vaccines does not mean they are unlicensed – they are licensed for use in different people or to be used in a slightly different way from the license recommendation.

Often, the information gained from off-label use is then used by the manufacturer to apply to modify the license to include these different uses.

Examples of successful off-label vaccine use

Whooping cough vaccine for pregnant women

One example is the use of a whooping cough vaccine in pregnant women. In the years up to 2012, the UK experienced an increase in the number of whooping cough cases – many in babies too young to be vaccinated themselves. An urgent decision on how best to prevent deaths and serious illness in these babies was required.

In 2012, JCVI agreed that the best way to protect these very young babies was by vaccinating pregnant women with pertussis (whooping cough) vaccine. This would ensure that babies were born with high levels of antibody from their mothers.

There were 2 vaccines suitable for boosting whooping cough protection in adults but neither had been tested on pregnant women because pregnant women are excluded from most clinical trials. However, data on the extensive use of vaccines with similar components was available and suggested that the vaccine would be safe and effective. One of the vaccines was therefore offered ‘off-label’ to pregnant women and around 70% of mothers now receive the vaccine.

This vaccine programme quickly resulted in a significant fall in the number of whooping cough cases and deaths in babies and detailed analysis has shown that the vaccine is safe for the mother and the pregnancy. Based on the success of this vaccination programme, and particularly the important data on safety and effectiveness in pregnant women generated in the UK, regulators should now be able to determine if use in pregnancy will be ‘within label’ in the future.

Meningococcal B (MenB) vaccine for infants

In 2015, the MenB vaccine was introduced into the UK routine childhood schedule to protect babies against meningococcal B disease which is a major cause of meningitis and blood poisoning. The vaccine is licensed as a 3 dose schedule in babies aged 2 months, followed by a booster dose at around one year of age.

However, after expert consideration of all the available evidence, the JCVI recommended that 2 doses (at 2 months and at 4 months) with a booster (at 12 months) would protect babies was just as well as the licensed schedule. So one of the infant doses was dropped even though the license stated that 4 doses should be given. The schedule recommended by the JCVI is working well as around 250 cases of MenB disease were prevented in the first 3 years of the programme.

Human Papillomavirus (HPV) vaccine for teenagers

A further example is the HPV vaccine, which is given to 12 to 13 year-olds at school to protect them against cancers caused by infection with the Human Papillomavirus.

Based on studies in young adult women, the vaccine was originally given in 3 doses within a 6 month period. Subsequent studies, however, suggested that, in younger individuals, 2 doses, given 6 months apart, are as effective as the 3 dose course in young adults.

Based on the knowledge that younger individuals respond very well to vaccines and to make the programme work better with the school terms, JCVI recommended that the second dose of the HPV vaccine can be given between 6 and 24 months after the first, even though giving the second dose more than 6 months after the first dose is considered to be ‘off-label’.

Deciding when ‘off-label’ vaccines should be used

Sometimes, after the EMA or MHRA has licensed a vaccine, circumstances change – such as an outbreak of a disease which necessitates the vaccine being used in a different population. Sometimes, new data emerges, which the manufacturer may not have produced themselves, and so it is not yet reflected in the license.

For example, an independent study may show that the vaccine works just as well at a different schedule (for example, 2 doses 2 months apart instead of 3 doses at monthly intervals).

Such studies are often conducted independently to ensure that the vaccine fits into the existing UK schedule, avoiding additional visits or unnecessary injections. In these situations, a recommendation may need to be made that is different from the terms of the license, so that as many people as possible can benefit from the protection offered by the vaccine. For the national vaccine programme, these decisions are usually taken by the JCVI. Most commonly, they involve recommending that a vaccine that is licensed for one group of patients can be used ‘off-label’ in another age group, or that a vaccine may be used at a different schedule from that in the license.

Patient concerns about ‘off-label’ vaccine use

If individuals or parents have concerns about receiving an ‘off-label’ vaccine, they should be reassured that the vaccine is being given in this way following expert consideration by the JCVI or their healthcare professional that it is safe and effective to give it in this way and that there is a good reason to do so.

Not receiving a recommended vaccine could put themselves or their child at risk of contracting a serious infection.

More information

The Medicines and Healthcare products Regulatory Agency (MHRA) has comprehensive information on this topic, available via GOV.UK.

The General Medical Council also provides information about prescribing in their ethical guidance.