Regulatory events

Medicines under additional monitoring

The European Union (EU) has introduced a new process to label medicines that are being monitored particularly closely by regulatory authorities. These medicines are described as being under 'additional monitoring'. The concept of additional monitoring was introduced by the new EU laws on the safety-monitoring of medicines, the pharmacovigilance legislation, which started to come into effect in July 2012.

Medicines under additional monitoring have a black inverted triangle displayed in the package leaflet and in the information for healthcare professionals (called the summary of product characteristics) together with a short text explaining what it means.

The black triangle will be used in all EU Member States to identify medicines under additional monitoring. It will start appearing in the package leaflets of the medicines concerned from the autumn of 2013. Please note that it will not be displayed on the outer packaging of medicines.

What does the black triangle mean?  

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All medicines are carefully monitored after they are placed on the EU market. If a medicine is labelled with the black triangle, this means that it is being monitored even more intensively than other medicines. This is generally because there is less information available on it than on other medicines, for example because it is new to the market or there is limited data on its long-term use. It does not mean that the medicine is dangerous.

Additional monitoring status is always applied to a medicine in the following cases:

  • it contains a new active substance;
  • it is a biological medicine, such as vaccines or medicines derived from plasma (blood);
  • it has been given a conditional approval (where the company that markets the medicine must provide more study data about it) or approved under exceptional circumstances (where there are specific reasons why the company cannot provide a comprehensive set of study data);
  • the company that markets the medicine is required to carry out additional studies: for instance, to provide more data on long-term use of the medicine, or on a rare side effect seen during clinical trials.

The Agency's Pharmacovigilance Risk Assessment Committee (PRAC) can also decide to place any other medicine under additional monitoring, in cooperation with EU Member States.

European list of additionally monitored medicines

The PRAC maintains a list of medicines under additional monitoring in the EU, which it updates every month. For more information, see the list of medicines under additional monitoring.

Additional monitoring status may be assigned to a medicine when it is approved for the first time or at any time during its life cycle. A medicine remains under additional monitoring for 5 years or until the PRAC decides to remove it from the list.

There may be a delay between the Agency's decision to add or remove a medicine from this list and the time when the updated package leaflet comes into circulation. This is because it takes some time for the updated package leaflet to be printed and to gradually substitute older versions already on the market.

In case of any uncertainty, always check the list on the Agency’s website, which is reviewed every month and is constantly up-to-date.

Regarding orphan medicinal products (rare diseases):

Brand name


Indicated for



Brentuximab vedotin

Hodgkin lymphoma ORPHA98293

New active substance, conditional authorisation, PASS1



MPS 1   ORPHA579

Authorised under exceptional circumstances, PASS



Leukemia, Lymphocytic, Chronic, B-Cell   ORPHA67038

Conditonal authorisation, PASS



Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ORPHA99860

Authorised under exceptional circumstances



chronic myeloid leukaemia (CML), ‘Philadelphia-chromosome-positive’    ORPHA521

New active substance, conditionial authorisation, PASS


Histamine dihydrochloride

Leukemia, Myeloid, Acute   ORPHA519

Authorised under exceptional circumstances


c1 inhibitor, human

adults and adolescents with hereditary angioedema ORPHA91378




Leukemia, Myeloid ORPHA519

New active substance



Myoclonic Epilepsy, Juvenile   ORPHA307

Conditional authorisation



Mucopolysaccharidosis II ORPHA580

Authorised under exceptional circumstances



Idiopathic Pulmonary Fibrosis   ORPHA2032

New active substance, PASS



Precursor Cell Lymphoblastic Leukemia-Lymphoma  ORPHA99860   ORPHA99861

Authorised under exceptional circumstances



Iron Overload beta-Thalassemia   ORPHA848




Lambert-Eaton Myasthenic Syndrome ORPHA43393

Authorised under exceptional circumstances, PASS


Alipogene tiparvovec

Hyperlipoproteinemia Type I ORPHA411

New active substance, Authorised under exceptional circumstances, PASS



Cryopyrin-associated Periodic Syndromes ORPHA208650

Authorised under exceptional circumstances, PASS



Laron Syndrome ORPHA633

Authorised under exceptional circumstances, PASS



Myeloproliferative Disorders ORPHA824 ORPHA729 v

New active substance, PASS



Cystic Fibrosis ORPHA586

New active substance, PASS



Mucopolysaccharidosis VI ORPHA583

Authorised under exceptional circumstances, PASS


Concentrate of proteolytic enzymes enriched in bromelain


New active substance, PASS

Pomalidomide Celgene
Pomalidomide  Multiple Myeloma New active substance, PASS



Injections, Spinal Pain ORPHA95426

Authorised under exceptional circumstances, PASS


Agalsidase alfa

Fabry Disease ORPHA324

Authorised under exceptional circumstances, PASS



Malabsorption Syndromes

New active substance, PASS



Hypopituitarism   ORPHA90695

New active substance



Astrocytoma  ORPHA94

Conditional authorisation



Amyloidosis ORPHA69

Authorised under exceptional circumstances, New active substance, PASS



Thrombocythemia, Essential   ORPHA3318

Authorised under exceptional circumstances



Ovarian Neoplasms Sarcoma ORPHA213512

Authorised under exceptional circumstances


1PASS: Post-authorisation safety study. A study designed to confirm, further characterise or refute a safety signal which has been associated with a specific drug.

Why are medicines monitored after they are approved?

Regulators decide to authorise medicines after assessing their benefits and risks based on the results of clinical trials. Only medicines whose benefits have been shown to be greater than their risks can reach the market. This ensures that patients can access the treatments they need without being exposed to unacceptable side effects.

Clinical trials involve a relatively small number of patients for a limited period of time. Patients in clinical trials are carefully selected and followed up very closely under controlled conditions. In a real-life setting, a larger number of patients will use the medicine; they may have other diseases; and they may be taking other medicines. Some less common side effects may only occur once a medicine has been used for a long time by a large number of people. It is therefore vital that the safety of all medicines continues to be monitored while they are in commercial use.

Information is continuously collected after a medicine is placed on the market to monitor real-life experience with the product. European regulatory authorities closely monitor this information to make sure that the benefits of medicines continue to outweigh their risks. The same monitoring methods are used across the EU so that European regulators can share the information gathered in individual EU countries. This provides a wealth of knowledge for regulators to rely upon when making decisions, and enables them to act quickly to ensure patient safety when required, such as providing warnings to patients and healthcare professionals or restricting the way a medicine is used.

Reporting side effects

Reporting suspected side effects is an important way to gather more information on medicines on the market. Regulators look at reports of side effects alongside all the information they already have to make sure that the benefits of medicines remain greater than their risks and to take any necessary action.

The Agency encourages patients and healthcare professionals to report any suspected side effects directly to the health authorities in their country. Under the new pharmacovigilance legislation, patients have the right to report suspected side effects directly to the national authorities if they wish. Information on how to report suspected side effects is given in each medicine’s package leaflet and summary of product characteristics.

The black triangle is a way to quickly identify medicines that are subject to additional monitoring. Patients and healthcare professionals are strongly encouraged to report suspected side effects with medicines displaying the black triangle, so that any new emerging information can be analysed efficiently.

Introduction of the new European system

The black triangle will be introduced on 1 September 2013. Any new medicine authorised after this date which is subject to additional monitoring will include the black symbol in the package leaflet and the summary of product characteristics when it is placed on the EU market.

The legislation affects medicines authorised in the EU after 1 January 2011. Therefore, there will be a transition period while the package leaflets and summaries of product characteristics for these medicines are updated and eventually substitute the older versions on the EU market.

To confirm whether a medicine is subject to additional monitoring, always check the list on the Agency’s website, which is reviewed every month and is constantly up-to-date.

Page created: 25/04/2013
Page last updated: 16/10/2013
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