Black Triangle: Additional Monitoring of Medicines

Advice for Pharmacists

Why do we need pharmacovigilance?

In order for a medicine to be authorised by a regulatory authority for use in the UK, the benefits and risks of a medicines are carefully considered. It is impossible for absolutely all information about a medicine to be known prior to it obtaining a marketing authorisation, so a balance must be struck between making a new medicine available to patients and having adequate information on a product's safety and efficacy. Once a medicine is launched, ongoing safety monitoring is crucial, because at the time the marketing authorisation is granted the medicine will have been tested in a relatively small number of patients for a limited amount of time in clinical trials.

Patients participating in clinical trials are selected carefully and followed closely under tightly controlled conditions. However, once a medicine receives its marketing authorisation and is subsequently placed on to the market by a company, it will be available for use in a wider range of healthcare settings and in patients who may differ from the study population, for example ethnicity, age, and genetic background. It is possible that rarer adverse reactions may only start to be reported once the medicine has been used in a larger number of patients and/or over a long period of time. In addition, some patients may also be taking several other medicines and/or using complementary and alternative therapies which may result in new or unexpected drug-drug interactions being identified. Therefore, it is important to be able to identify any new or changing risk associated with a medicine quickly.

The aim of this document is to explain how a specific pharmacovigilance activity, the black triangle, is used to monitor the safety and efficacy of new medicines after they are placed on the market.

What is the black triangle?

The black triangle has been running in the UK for many years to highlight medicines that are subject to intensive safety monitoring. The black triangle aims to ensure that the safety of any new medicine is monitored closely. Since 2013 the black triangle has become part of an EU wide scheme and is now known as additional monitoring.

The scheme ensures that the same monitoring methods are used EU wide, so that European regulatory authorities can share the information from the individual EU countries. This provides larger amounts of information for regulators to evaluate when making decisions, and enables them to act quickly to ensure patient safety is protected, when required. For example, regulators can alert patients and healthcare professionals about newly established warnings and special precautions associated with the use of a product or they may restrict the way a medicine is used.

Why do new medicines require additional monitoring?

At the time a new medicine becomes available clinical trials have provided relatively little safety information on the medicine meaning that only the more common adverse effects of treatment are likely to be identified. Therefore, effective drug surveillance after marketing is crucial for the identification of rare adverse effects, and to ensure that appropriate action is taken.

What does a black triangle on a medicine mean?

Medicines under additional monitoring carry a black triangle symbol (an inverted equilateral black triangle (▼)).The black triangle alerts both patients and healthcare professionals (HCPs) that the medicine is being closely monitored by European regulatory authorities. The black triangle is a mechanism to strengthen monitoring and to actively encourage patients and HCPs to report any possible adverse reactions observed with these medicines. The black triangle symbol does not mean that a medicine is unsafe for use in patients, it just highlights that all information on the safety of the product should be gathered.

On what medicines can I expect to find a black triangle?

A black triangle is assigned to a new medicine when it is approved for the first time. The black triangle is assigned irrespective of how the medicine has been authorised, i.e. either authorised centrally through the European Medicines Agency (EMA) or nationally through the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK, and is assigned to medicines that fall into the following categories:

  • Medicines that contain a new active substance that was not contained in any authorised medicine in the EU on 1 January 2011;
  • Biological medicines authorised after 1 January 2011 - this applies to all biological medicines including biosimilars, vaccines and medicines derived from plasma;
  • Medicines for which the marketing-authorisation holder is required to carry out a post-authorisation safety study (PASS); this type of study is carried out after a medicine has been authorised and is designed to obtain further information on a medicine's safety, or to measure the effectiveness of risk-management measures;
  • Medicines given conditional approval or authorised under exceptional circumstances, for example medicines to treat very rare conditions or because collection of full information is not possible or is unethical, and medicines authorised with specific obligations on the recording or monitoring of suspected adverse drug reactions e.g. a controlled access scheme.

It is important to note that other medicines can also be placed under additional monitoring, based on advice from the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC).

What types of suspected adverse reactions should be reported for black triangle medicines?

In the UK the Commission on Human Medicines (CHM) and the MHRA encourage the reporting of all suspected adverse reactions (side effects) to newer medicines, i.e. those containing drugs as well as vaccines, which are denoted by the black triangle symbol (▼). Pharmacists, other HCPs and patients are encouraged to report any suspected adverse reaction for black triangle medicines, however minor.

For biologicals (including biosimilar medicines), adverse reaction reports should clearly state the brand name and the batch number of the suspected medicine.

Reports can be submitted via the Yellow Card Scheme at: Yellow Card Scheme - MHRA Yellow card and/or directly to the marketing authorisation holder.

Where will I see the black triangle symbol?

Marketing-authorisation holders of medicines subject to additional monitoring are required to ensure that the product information includes the black triangle symbol and to ensure that it is displayed next to the name of a relevant product in the following places:

  • in the British National Formulary (BNF)
  • in the British National Formulary for Children (BNFC)
  • in Monthly Index of Medical Specialties (MIMS)
  • on the electronic Medicine Compendium (eMC)
  • on advertising material
  • in Drug Safety Update (a monthly newsletter from the MHRA that provides the latest information and advice on drug safety issues to healthcare professionals etc.)
  • Summaries of Product Characteristics (SmPC/SPC) and Patient Information Leaflets (PIL)

In some instances it is accompanied by a short sentence of explanation to describe what the black triangle symbol means. For example, the PIL will contain the following wording:

▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See the end of section 4 for how to report side effects.

The black triangle symbol does not appear on the outer packaging of medicines.

How long does a medicine have a black triangle symbol and under what circumstances will it be removed?

Typically new medicines are assigned a black triangle for a period of five years following first authorisation in the EU. In some cases the period may be longer than five years e.g. if there are ongoing safety concerns, or to complete PASS studies. The decision to remove the medicines from the additional monitoring list must be agreed by the EU regulators following which there may be a delay before updated product information is available. i

The black triangle can also be assigned or re-instated in some cases at later stages of a medicine's life cycle if a new safety concern has been identified that requires monitoring.

What roles can pharmacists play in handling black triangle medicines?

Pharmacists should be aware of the significance of a black triangle symbol on a medicine. Pharmacists should be vigilant and report all suspected adverse drug reactions for black triangle medicines using the Yellow Card Scheme and/or by contacting the marketing authorisation holder directly. Pharmacists can also help support and educate patients and answer any questions they may have regarding the black triangle as well as assisting patients with the completion of Yellow Card reports.

Pharmacists should be familiar with any risk minimisation materials a medicine may have and ensure that they are distributed to patients and that patients are counselled on the use of these medicines.

Pharmacist can keep up to date with the list of medicines under additional monitoring by checking the information on the EMA website. ii

Where will I find information on which medicines are subject to additional monitoring?

The EMA is responsible for updating and maintaining the list of medicines that require additional monitoring (black triangle products) and this list is reviewed each month by the EMAs Pharmacovigilance Risk Assessment Committee (PRAC) and updated as required.

The MHRA website also contains a link to the updated list of medicines that are subject to additional monitoring.

References

i Guideline on good pharmacovigilance practices (GVP), Module X – Additional monitoring

ii List of medicines under additional monitoring

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