Pharmaceutical product drug ingredients and medical device(s)

Section 2. Qualitative and Quantitative composition of the SmPC and section 6.1. List of excipients of the SmPC indicate the composition of pharmaceutical product(s) within the medicinal product.

Each pharmaceutical product must contain information on:

• Active ingredient(s) - active ingredient substance name(s) and its/their concentration(s) can be found in section 2. Qualitative and Quantitative Composition of the corresponding SmPC;

• Excipient(s) - excipient substance name(s) can be found in section 6.1 List of excipients of the corresponding SmPC. It is optional to submit the concentration(s) of excipient(s);

• In some instances, pharmaceutical product can also contain adjuvants. Adjuvant substance name(s) and its/their concentration(s) can be found in section 2. Qualitative and Quantitative Composition of the corresponding SmPC.

Pharmaceutical Product active ingredient element structure:

Pharmaceutical Product excipient element structure:

Pharmaceutical Product adjuvant element structure:

Detailed guidance on the electronic submission of information on medicinal products for human use by marketing authorisation holders to the European Medicines Agency in accordance with Article 57(2) of Regulation (EC) No. 726/2004

EMA/135580/2012 Page 80/180

Pharmaceutical Product medical device element structure

NOTE 9

Only approved substances can be referenced in a pharmaceutical product within an authorised medicinal product entity.

Each approved substance successfully submitted in the XEVMPD has an assigned EV Code. The preferred name of the approved substance is entered in English. Each translation and synonym are linked to the master substance EV Code.

The substance name used in the pharmaceutical product must be in line with the substance name used in the SmPC and should provide the description of the substance within the medicinal product

irrespective of national naming convention or any symbols, commas, and additional brackets, hyphens.

• If a substance name was previously successfully submitted in the XEVMPD and a substance EV Code has been assigned, the substance name can be selected from the available EudraVigilance look-up table (EVWEB users). Gateway users should populate the 'Active ingredient substance code' field (PP.ACT.1) with the assigned substance EV Code.

List of available approved substances with their assigned EV Codes can be found in the XEVMPD look-up table/Controlled Vocabulary (CV) lists published on the Agency's website - see "eXtended Eudravigilance Product Dictionary (XEVMPD) substances". The published XEVMPD substance controlled vocabulary list contains substances available at the time of publication.

The EudraVigilance look-up table contains the most up-to-date data as substance information is submitted to the XEVMPD on daily basis.

• If a new approved substance/substance translation or a synonym/alias needs to be submitted in the XEVMPD please follow the process described in the communication Changes to some business rules of the eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD): Submission of substance information or in section 1.4. Initial submission of an approved substance of this document.

EXAMPLE 42

Scenario 1 – Exact substance name is not available in the XEVMPD look-up table/published Controlled Vocabulary (CV) list but a similar substance name is listed

Section 6.1. List of excipients of an English SmPC states "IRON OXIDE BROWN (E-172)". The substance name as stated in the SmPC is not present in the XEVMPD look-up table/published

Controlled Vocabulary (CV) list. However, an approved substance with a preferred name "IRON OXIDE BROWN (E172)" is available with EV Code SUB130375 and should therefore be referenced in the pharmaceutical product. A request for addition of "IRON OXIDE BROWN (E-172)" as a synonym to SUB130375 should be submitted to the Agency as a request logged with the EMA Service Desk portal (https://servicedesk.ema.europa.eu/). The Agency will process the request in the XEVMPD and provide the MAH with the master substance EV Code to be referenced in their product entry.

Section 2. Qualitative and Quantitative Composition of an English SmPC states "VORTIOXETINE D,L-LACTATE". The substance name as stated in the SmPC is not present in the XEVMPD look-up table/published Controlled Vocabulary (CV) list. However, an approved substance with a preferred name "VORTIOXETINE (D,L)-LACTATE" is available with EV Code SUB130400 and should therefore be referenced in the pharmaceutical product. A request for addition of "VORTIOXETINE D,L-LACTATE" as a synonym to SUB130400 should be submitted to the Agency as a request logged with the EMA Service Desk portal (https://servicedesk.ema.europa.eu/). The Agency will process the request in the XEVMPD and provide the MAH with the master substance EV Code to be referenced in their product entry.

Detailed guidance on the electronic submission of information on medicinal products for human use by marketing authorisation holders to the European Medicines Agency in accordance with Article 57(2) of Regulation (EC) No. 726/2004

EMA/135580/2012 Page 82/180

Scenario 2 – Substance name is not available in the XEVMPD look-up table/published Controlled Vocabulary (CV) list

Section 6.1. List of excipients of a Czech SmPC states "Sepifilm 3011 oranžová", which is a translation of substance name "Sepifilm 3011 Orange". Neither the substance name as stated in the SmPC nor the preferred name in English is present in the XEVMPD look-up table/published Controlled Vocabulary (CV) list. A request for addition of a new preferred substance name and a translation should be submitted to the Agency as a request logged with the EMA Service Desk portal

(https://servicedesk.ema.europa.eu/). The Agency will process the request in the XEVMPD and provide the MAH with the master substance EV Code to be referenced in their product entry.

Section 6.1. List of excipients of a French SmPC states "laque aluminique de rouge cochenille A (E124)", which is a translation of substance name "aluminium lake red cochenille A (E124)". Neither the substance name as stated in the SmPC nor the preferred name in English is present in the XEVMPD look-up table/published Controlled Vocabulary (CV) list. A request for addition of a new preferred substance name and a translation should be submitted to the Agency as a request logged with the EMA Service Desk portal (https://servicedesk.ema.europa.eu/). The Agency will process the request in the XEVMPD and provide the MAH with the master substance EV Code to be referenced in their product entry.

NOTE 10

If a pharmaceutical product contains no active ingredient, one of the excipients and its strength should be selected and entered as the active ingredient. The substance selected as the active ingredient should not be entered also as an excipient as this would result in receiving a negative XEVPRM acknowledgement due to duplication of the same substance within one pharmaceutical product.

When a substance contains multiple components, both the substance and the individual components should be submitted, providing that the substance has a descriptive level of information relevant to excipient in medicinal products (e.g. general terms not indicative of excipients in medicines are not accepted such as thickeners, ink, emulsifiers).

EXAMPLES:

• Thickeners (methylcellulose, xanthan gum);

• Stearate emulsifiers (polyethylene glycol sorbitan tristearate, macrogol stearate, glycerides);

• lemon flavour (maltodextrin, arabic gum, lactose, triethyl citrate).

In the authorised product entity, all of the substance names should be referenced separately since they are substance names referenced in an approved SmPC; i.e. methylcellulose, xanthan gum, stearate emulsifiers, polyethylene glycol, sorbitan tristearate, macrogol stearate, glycerides, lemon flavour, maltodextrin, arabic gum, lactose and triethyl citrate.

Further guidance on how to handle approved substance names is included in the 'EMA Substance names best practice' document published in section "Data Quality-control methodology" on the Agency's webpage.