Marketing authorisation holders and applicants need to identify the excipients included in any human medicine authorised in the European Union (EU) in its product information. Guidance is available from the European Commission and European Medicines Agency (EMA) on what needs including in the labelling and package leaflet.
An excipient is a constituent of a medicine other than the active substance, added in the formulation for a specific purpose. While most excipients are considered inactive, some can have a known action or effect in certain circumstances. These must be declared in the labelling and package leaflet of the medicine for its safe use.
The legal basis for requirements on excipient labelling in the EU is Article 65 of Directive 2001/83/EC.
Marketing authorisation holders and applicants should list excipients on the medicine's labelling and in the package leaflet in line with the following European Commission guideline:
This guideline requires marketing authorisation holders to display excipients in the following ways:
|Type of excipient||Type of medicine||Type of information||Display location|
|All excipients||All medicines||List of excipients||Package leaflet|
|Parenteral, ocular and topical medicines||List of excipients||Labelling|
|Excipients with a known action or effect||All medicines||List of excipients||Labelling|
|Agreed safety information||Package leaflet|
These requirements apply to all medicines in the EU, irrespective of whether they are centrally or nationally authorised.
The list of excipients that have a known action or effect, and which must appear on the labelling of all medicines in the EU, is available in the annex to the above EU guideline:
The annex also includes the safety information that must appear in the medicine's package leaflet for the listed excipients. It is available in all EU languages, Icelandic and Norwegian.
EMA may revise the annex to update the required safety information on existing excipients, or to add new excipients. Revisions of the annex are endorsed by the European Commission.
For authorised medicines, marketing authorisation holders should use the first opportunity to implement any revised wording in the package leaflet.
For medicines with no foreseeable regulatory submissions, marketing authorisation holders should submit a type IB variation within 3 years of the revision date of the relevant excipient.
Marketing authorisation holders can find the revision date for a particular excipient in the column ‘updated on’, next to the excipient's name in the annex.
Background information supporting the EU requirements for individual excipients can be found on the relevant webpages, which are listed below.
- Aspartame and phenylalanine
- Benzalkonium chloride
- Benzoic acid and benzoates
- Benzyl alcohol
- Boric acid and borates
- Fragrances containing allergens
- Fructose and sorbitol
- Propylene glycol and esters
- Sodium used as an excipient in medicinal products for human use
- Sodium laurilsulfate
- Wheat starch containing gluten