Questions and answers SPC

As of the coming into effect of Regulation (EU) 2019/6, the requirement to indicate the so-called blue box requirements (former national requirements, in case of the Netherlands: the registration number and legal status of supply) on the label of the outer packaging and the label of the primary packaging has expired. Regulation (EU) 2019/6 does not allow Member States to require additional information on the packaging/labels.

However, the label of the outer packaging must bear a registration number. For veterinary medicinal products authorised by the national procedure, decentralised procedure or mutual recognition procedure, this is the Dutch registration number (‘REG NL number’). For VMPs authorised through the central procedure, this is the central registration number. The label for primary packaging or the label for small primary packages shall not bear a registration number. The legal status of supply is not indicated on any label. The national legal status of supply in the Netherlands is only mentioned in the package leaflet.

In the Netherlands, an identification code should be added to the outer packaging and the primary packaging. The identification code shall not replace the registration number on the outer packaging. As long as there is no implementing act of the European Commission laying down uniform rules for the identification code, marketing authorisation holders should use the European Article Numbering Code (EAN code) as an identification code. The EAN code only needs to be placed on the outer packaging.

The national legal status of supply in the Netherlands is only mentioned in the package leaflet. In accordance with Article 14(2) of Regulation (EU) 2016/6, the legal status of supply should be clearly separated from the information required by the Regulation in the package leaflet. A black square is included in the QRD template version 9.0 for this purpose. The legal status of supply is indicated in the QRD template in this black square.

For the following question regarding the inclusion of national information on the blister, I would like to refer to:

• Regulation (EU) 2019/6, Article 12
• QRD template 9.0, A. Labelling, MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

In the Regulation, Article 12, you can read that a small package must contain no information other than the information prescribed in the Regulation (this also applies to outer packaging and primary packaging, see Articles 10 and 11). As described in the Regulation and QRD template 9.0, the blister should therefore only indicate the invented name of the product, active substance quantitatively per unit, batch number, expiration date and shelf life after opening. REG NL number and legal status of supply are therefore not allowd on the blister, unless the MAH submits a request to the Agency for Veterinary Medicinal Products in accordance with Article 13 of the REGULATION(EU) 2019/6 and the Veterinary Medicines Agency approves this request.

In the Netherlands, the Veterinary Medicinal Products Regulation 2022 has been published to bring national legislation into line with Regulation (EU) 2019/6. In this, national implementations have been given to the points in which the Regulation provides scope for national legislation:

• In accordance with Regulation (EU) 2019/6 Article 10.3 and Article 11.2, which states that Member States may choose to make an identification code on the outer packaging and primary packaging mandatory, the Veterinary Medicinal Products Regulation 2022 stipulates that an identification code on the outer packaging and primary packaging is required in the Netherlands. Transitional law shall apply: as long as the European Commission has not yet published an implementing act to establish uniform rules for the identification code (see REGULATION(EU) 2019/6 Article 17.1), it is only necessary to state the EAN code to the outer packaging.
• According to REGULATION(EU) 2019/6 Article 14.2, the package leaflet may contain additional information on distribution, possessions, precautions as long as the information does not concern promotion/advertising (a black square is included in the QRD template at the bottom of the package leaflet). The Regulation on Veterinary Medicinal Products 2022 states that the inclusion of the legal status of supply in the package leaflet is mandatory.

So briefly summarised:

• The REG NL number for NP/DCP/MRP products is present on the outer packaging and in the package leaflet (under the fixed headings for the registration number). For CP, the EU registration number is mentioned here, CP products no longer state the REG NL number in the printed material. No registration number shall be stated on primary packaging/small unit packets.
• For NP/DCP/MRP/CP, the legal status of supply is clearly separated from the information prescribed by the Regulation. The legal status of supply is not mentioned on any packaging.
• An identification code is required on the outer packaging and primary packaging, but as long as the EC has not yet published an implementing act on it (and therefore it is not clear how it should look), only the EAN code should be stated on the outer packaging.

There is no regulation or policy agreement regarding the provision of the electronic package leaflet. In general, it can be said that the package leaflet made available digitally should be made readily accessible to the user. For example, a QR code could be used.

It is not possible to suffice with only English-language packaging and package leaflets combined with a Dutch information leaflet.

Art. 7 of Regulation 2019/6 states:

1. The language or languages ​​of the summary of the product characteristics and the information on the label and in the package leaflet is, unless the Member State determines otherwise, an official language or languages ​​of the Member State in which the veterinary medicinal product is the market is offered.

2. Veterinary medicinal products may be labeled in several languages.

The policy agreement in relation to Article 7 paragraph 1 of Regulation 2019/6 is that, in principle, the SPC and the packaging and package leaflet texts of veterinary medicinal products must be in Dutch.

In the event of an availability problem with a veterinary medicinal product, in the event of temporary shortages or in the event that the veterinarian applies the veterinary medicinal product, an exception can be made. In that case, packaging in another language may be permitted in combination with a Dutch-language package leaflet. An MAH can submit a substantiated request for an exception to the Veterinary Medicinal Products Unit.

The Animals Act does not state how long a veterinary medicinal product may be delivered after changing the product information (SPC, labelling and package leaflet) or after amendment of the file information associated with the marketing authorisation.

For veterinary medicinal products authorised through the national, decentralised or mutual recognition procedure, the policy agreement shall be that after publication of the decision in the Veterinary Medicinal Products Information Bank under ‘Nieuwe of niet meer toegelaten handelsvergunningen in vrij op te geven tijdvak’ till the amendment of the marketing authorisation:

The manufacturer is not allowed to manufacture the veterinary medicinal product with unchanged product or dossier information (labelling and package leaflet) and;

The existing stock of batches already released with unchanged product or file information (labelling and package leaflet) will be delivered to wholesale and/or retail stores within 6 months.

This is sometimes deviated from when the variation is the result of, for example:

• A restriction of efficacy;
• An adaptation to safety;
• A change in the quality of the veterinary medicinal product.

In this case, the existing stock with the manufacturer may need to comply directly with the amended product information (SPC, labelling and package leaflet). The Veterinary Medicines Agency adopts this amended product information (SPC, labelling and package leaflet) on behalf of the Minister of Agriculture, Fisheries, Food Security and Nature.

For centrally authorised veterinary medicinal products, the implementation period of the EMA is followed. This is six months by default, but in special cases, the EMA and the Commission may decide to deviate from this term.

For the single G.I.18 variation that requires assessment to update the product information to the QRD template version 9.0, it has been decided that the Commission will include an implementation period of 12 months in their decisions. This does not apply to grouped variations where the G.I.18 variation is combined with another variation. Also, when another variation for the same veterinary medicinal product is approved during the implementation period, which should be implemented earlier than the single QRD 9.0 update, the implementation of this variaton must already be done in QRD version 9.0.

For single updates of the QRD template to version 9.0 for products authorised via the national, decentralized or mutual recognition procedure, an implementation period of 12 months can also be requested in the application form.

According to the QRD template (currently version 9, 03/2022 corr. 11/2022), the name of a veterinary medicinal product is built up as follows:

‘(Invented) name of veterinary medicinal product <strength> pharmaceutical form <target species>’

As indicated in the QRD template itself, the brackets &...> mean “Text to be selected or deleted as appropriate.” So depending on whether it is necessary or not, the target species may or may not be mentioned in the name of the veterinary medicinal product. The QRD template provides further explanations on target animal species in the name of the veterinary medicinal product:

if necessary, target species, in order to avoid any confusion over different presentations of the veterinary medicinal product (e.g. same active substance and invented name) in different formulations for different target species. Indicate species in singular or plural as per official language.

Target species: taking into account the target species list under “Referentials” on the SPOR website

http://spor.ema.europa.eu/rmswi/#/lists/100000108853/terms]»

Thus, in the event that there may be uncertainty for which animal the product is intended, e.g. because different formulations for different animal species with the same trade name are placed on the market, the target species should be mentioned in the name. If there is no risk of confusion between veterinary medicinal products with the same or similar names intended for different target species, including target species in the name is not considered necessary.

The SPC and package leaflet shall contain the full name of the veterinary medicinal product, including target species if included in the name. The label shall indicate the target species not in the name but separately under the heading ‘target species’. On the printed labels, the target animal species should be presented near the name of the veterinary medicinal product.

For every known adverse event, look for the best matching VeDDRA (Veterinary Dictonary for Drug Regulatory Activities) low level term. The combined list for VeDDRA terms in humans and animals can be found here.

Per adverse event (VeDDRA low level term) determine the frequency in which the adverse event occurs, and you place the adverse event in the correct row in the table. For the purpose of determining the frequency, preferably use the frequency as observed in safety studies for the veterinary medicinal product (or in the case of a generic: as observed for the reference veterinary medicinal product). If the adverse reaction is known only from reports of suspected adverse reactions following market authorisation (pharmacovigilance), this data can be used to determine the frequency. Is it impossible to determine a frequency because the adverse events have never been found, or for a generic because there is no frequency in the SPC of the reference product? Then an additional row can be added to the table with the category “Undetermined frequency”.

Per frequency, the VeDDRA low level terms belonging to the same System Organ Class (SOC) are grouped. In the combined list for VeDDRA terms in humans and animals you can see to which SOC a VeDDRA low level term belongs to.

Additional information, e.g. on the severity, duration or treatment of the adverse reaction, is preferably presented with a footnote below the table. If footnotes are not used, additional information can also be added in parenthesis.

For further instructions for completing section 3.6 Adverse events of the SPC, please consult the EMA’s Q&A on AE description in PI — clean (europa.eu).

This section may specify restrictions or conditions referred to in Regulation (EU) 2019/6:

• Article 106(4): Member States may decide, if duly substantiated, that a veterinary medicinal product may only be used by veterinarians;
• Article 107(6): the Commission may adopt implementing regulations to prohibit the use of certain antimicrobials or to impose conditions of use;
• Article 110(1):  competent authorities may, in accordance with national law, prohibit the manufacture, import, distribution, possession, sale or supply of immunological veterinary medicinal products in their territory or part thereof.

If no restrictions on use or conditions of use have been established for the veterinary medicinal product, you can fill in the section with “Not applicable”.

The classification of the veterinary medicinal product shall indicate whether it is a ‘veterinary medicinal product subject to prescription’ or a ‘veterinary medicinal product not subject to prescription’. This section does not specify the national legal status of supply (a further subdivision of veterinary medicinal products under prescription applicable nationally in the Netherlands).

Regulation (EU) 2019/6 indicates that no information other than the information required by the Regulation should be included on the outer packaging, the primary packaging and the small primary packaging. By way of exception, applicants may submit a request to the competent authority to place on the outer packaging or primary packaging additional useful information that corresponds to the SPC and does not concern advertising. This is stated in Article 13 of the Regulation. Requests may be submitted to the Veterinary Medicinal Products Agency. 

At the time of the European stage of a procedure, the headings in section 16 of the package leaflet concerning the marketing authorisation holder, local representative, and the contact details where adverse events can be reported (the marketing authorisation holder or the local representative) can be left empty in the harmonised English-language product information. This is because these organisations may differ between Member States, and the harmonised English text should apply to all Member States. However, the manufacturer(s) responsible for release is already entered in section 16 at this stage of the procedure as it is/are the same for all Member States.

Translations are provided to Member States during the national implementation phase and in these translations, the national marketing authorisation holder and the contact details to report updates or, if necessary, a local representative where adverse reactions can be reported in that Member State can be reported.

The ‘local representative’ is referred to in Article 77(3) of Regulation (EU) 2019/6: ‘The marketing authorisation holder shall designate a local or regional representative who receives the reports of suspected adverse effects and is able to communicate in the languages of the relevant Member States.’

It is therefore important to distinguish between a distributor and a local representative. A distributor shall not be listed as a ‘local representative’ in the package leaflet if it does not accept adverse reactions reports for the marketing authorisation holder.

The distributor may be the local representative who accepts reports of adverse reactions in the national language of the Member State, but it may also be that a marketing authorisation holder has a separate distributor and local representative, or that the marketing authorisation holder has a distributor in a given Member State, but that the reports of adverse reactions in that Member State can be made directly to the marketing authorisation holder.

Background information

Harmonisation of the SPCs for nationally authorised veterinary medicinal products is set out in Articles 69 to 72 of the Regulation (EU) 2019/6. Harmonisation of SPCs is only possible for:

• Reference veterinary medicinal products authorised nationally in different Member States, with the different national marketing authorisations having the same qualitative and quantitative composition and pharmaceutical form and of the same marketing authorisation holder.
• Generics and hybrid veterinary medicinal products, the nationally registered reference product of which has undergone SPC harmonisation.

Three Best Practice Guides have been drawn up by the CMDv on SPC harmonisation:

• For the selection of veterinary medicinal products for SPC harmonisation (further elaboration of Article 70 of the VO, paragraphs 1 to 4)
• For the harmonisation of the SPCs of national reference veterinary medicinal products (further elaboration of Article 70 of the VO, paragraphs 5 to 12)
• For the harmonisation of the SPCs of generics/hybrids of harmonised national reference veterinary medicinal products (further elaboration of Article 71 of the VO)

Both marketing authorisation holders and competent authorities can nominate nationally authorised veterinary medicinal products for SPC harmonisation. Are you a marketing authorisation holder and would you like to nominate one of your veterinary medicinal products for SPC harmonisation? A web form is available to give up your veterinary medicine. Each year, a selection of VMPs will be made which will be harmonised the following year. The deadline for submitting nominations is on 31 May each year. At the end of each year, the list of veterinary medicinal products to be harmonised shall be published by the CMDv.

The timing of the submission of variations for SPC harmonisation shall take place in consultation between the RMS designated by the CMDv and the marketing authorisation holder. As after SPC harmonisation the national reference veterinary medicinal products as MRP veterinary medicinal products continue, in addition to the variation for SPC harmonisation, a variation for harmonisation of the quality part of the dossier is submitted. Once the SPC harmonisation for the national reference veterinary medicinal products has been completed, all marketing authorisation holders of the generics/hybrids using these national products as a reference product should also submit variations to harmonise their product information on target animal species, clinical information and withdrawal times with that of their reference product.

Current situation (answer to question)

The REGULATION(EU) 2019/6 entered into force in 2022. The SPC harmonisation procedure thus started in 2022 with the nomination of nationally authorised reference veterinary medicinal products. Subsequently, a selection was made of a number of VMPs that will be harmonised in 2023 and RMSs were designated by the CMDv’s SPC Harmonisation Working Group. This list has now been approved by the CMDv. Following approval by the HMA (expected in February 2023), the list will be published on the CMDv website and the SPC harmonisation of selected national reference products can be started.
Of course, national reference veterinary medicinal products can also be nominated for SPC harmonisation in 2023 (until 31 May 2023), if a nominee is selected for the list in 2023, then the SPC harmonisation of this product will be started in 2024.

It’s about whether the products belong to the same global marketing authorisation. So if the national authorisations belong to the same global company, but e.g. in the Netherlands the holder is ‘Company B.V.’ and in another Member State the holder is ‘Company S.A.’, these national reference veterinary medicinal products can be nominated for SPC harmonisation.

No, this is not possible for industry, only for competent authorities. A company can only nominate its own veterinary medicinal products.

Yes, it is indeed possible that this increases the thresholds, but since all variations following the SPC harmonisation have to be harmonised via MRP according to the Regulation, it is necessary to harmonize Part II.

The QR (quick response) code is a two-dimensional barcode. The QR code links to a website URL. The URL is encoded and printed on the outer packaging and/or the package leaflet of a veterinary medicinal product.

You scan the QR code using a QR reader (application) on a smartphone, for example. The app translates this scan to the URL, and the device’s browser opens the relevant website, giving you access to digital information about a certain veterinary medicinal product.

The QR code policy described below applies to all veterinary medicinal products for which a marketing authorisation of a veterinary medicinal product has been issued in the Netherlands. This policy is largely in line with the policy stated in the EMA guidance Quick Response codes, for veterinary medicinal products in the Centralised procedure.

This policy only relates to the use of QR codes that refer to web pages containing information about the relevant veterinary medicinal product. 2D barcodes that are used exclusively for internal production processes and that do not contain information about the veterinary medicinal product do not fall under the scope of this policy. The same approach applies for techniques that have the same function as the QR code.

For example, a QR code can refer to an electronic package leaflet. Under the Veterinary Medicinal Products Regulation (Regulation 2019/6), an EEA Member State may stipulate that the package leaflet be made available on paper or in electronic form, or both. In the Netherlands, the package leaflet may be made available on paper or in electronic form.

To place a QR code on the packaging and/or in the electronic and/or paper package leaflet, the conditions listed in Articles 13, 14 and 15 of Regulation 2019/6 must be met. This means that the Veterinary Medicinal Products Unit may, at the request of the applicant, authorise the inclusion of useful additional data on the primary or outer packaging and the package leaflet of a veterinary medicinal product which:

• are compatible with the statutory product information such as the data in the approved SPC, labelling and package leaflet, and;
• do not advertise for a veterinary medicinal product.

The format in which the information is provided can be determined freely, provided that the requirements for the information underlying the QR code have been met. The information is made available via the QR code by the marketing authorisation holder, who also ensures that this information is kept up to date on the relevant website.

A QR code may be included on the packaging and in the package leaflet, provided that the information required by law to be displayed on the packaging takes precedence in prominence and placement. In the case of small packaging, the QR code can also be positioned on the inside of the packaging.

If the veterinary medicinal product has a parallel import marketing authorisation, the QR code of the original supplier of the veterinary medicinal product must be covered with tape.

If you submit a first-time request for the inclusion of a QR code, you can submit this application during the procedure for the issue of the marketing authorisation or after this procedure has been completed.

Pre-authorisation – Procedure for simultaneous submission of a marketing authorisation application or variation

An initial request for the inclusion of a QR code at the time of application for a first marketing authorisation or a relevant variation will be assessed along with the application. The same procedure applies when additional information is provided. You must submit this information no later than during the national phase.

Post-authorisation – Procedure after the issue of a marketing authorisation

After the marketing authorisation has been issued, you have two options to add a QR code:

• Do you want to use a QR code to link only to the statutory product information? This means the product information exactly as approved and in the official language of the Member State.

Online statutory product information may consist of, for example, a PDF, web pages and web applications, or images of the product packaging exactly as they appear on the market. In that case, you only need to submit the QR code request form. In this form, you confirm that the content of the QR code complies with and will continue to comply with the relevant regulations.

• Would you like to provide additional electronic information about a veterinary medicinal product via a QR code? This means information that is consistent with the approved product information, but not word-for-word identical to the approved text. Examples include:
  • video clips or animated manuals, images or diagrams, not mentioned in the approved product information, showing how to administer/use the veterinary medicinal product;
  • links to report side effects.

If this is the case, you submit a variation, type VRA-R classification G.I.15 (z).

If the QR code only links to statutory product information, you should submit the QR code request form when applying for an initial marketing authorisation or a variation.

After this, you will receive a notification saying that:

• the QR code request has been received and that it is your responsibility as a market authorisation holder that the QR code request form is correctly completed and that the QR code links only to statutory information;
• the QR code can be added correctly (see below) to the printed packaging material;
• you must submit a Variation Requiring Assessment if the QR code links to more than just the approved product information;
• you must submit updated label and package leaflet texts in the next variation procedure affecting the product information, indicating 'QR code' + <URL> if applicable:
  • in the LABELLING after the last section (15) of the data appearing on the outer packaging; and/or
  • in the LABELLING after the last section (9) of the data appearing on the primary packaging; and/or
  • in the PACKAGE LEAFLET after the last section and, if applicable, before the separate box; or
  • on the COMBINED LABEL and the PACKAGE LEAFLET after the last section (21) of the data that need to be included on the primary packaging.

When requesting a QR code on the packaging and/or in the package leaflet, linked to additional information on a veterinary medicinal product, you must submit the following documentation (when applying for a marketing authorisation or a variation):

• an application form;
• the completed QR code request form, a copy of which will be issued to you after you have completed the form online;
• a description of and – if applicable – a visual representation of the information available to users via the QR code. You must make the contents available in folder '1a-admin-info' of the file for the purpose of assessment;
• an MS Word version of the product information contained in the QR code;
• for veterinary medicinal products authorised via the Centralised, Mutual-Recognition or Decentralised procedure, a Dutch translation of the additional information. For videos, you must submit a Dutch-language version or a translated video script (together with the English-language video and the English-language script).

If the variation only pertains to addition of the QR code, the variation is a VRA-R, classification G.I.15 (z).

If the statutory product information changes as a result of a VRA/VNRA, the statutory information linked to the QR code should be updated as well. No separate variation application or QR code request will be required in that case.

If the QR code itself changes (e.g. because the URL refers to a different location), a new QR code request via the QR code request form will be required.

If, after the QR code has been approved, you submit a VRA or VNRA updating the product information and also updating the additional information behind the QR code, there are two options:

• You provide – simultaneously with the VRA/VNRA (or no later than during the national phase) – the following modified documentation related to the QR code:
  • an updated QR code request form showing the changes;
  • a clear description and – if applicable – visual representation of the updated additional information available to users via the QR code.

In that case, no separate variation is required.

• Are you unable to also provide the updated additional information behind the QR code simultaneously with the VRA/VNRA (or at the latest during the national phase)? In that case, however, a separate VRA is required (G.I.15 (z)). 

For a safety-related change, you update the linked additional information, e.g. videos, immediately after approval. This is to ensure that outdated material does not remain in the public domain, as this could cause a less safe or less effective use of the veterinary medicinal product. So here, the QR code on the packaging/package leaflet does not change, but the content behind the QR code does.

If you want to change the additional information provided via the QR code in another context, i.e. not as a result of a marketing authorisation variation, a standalone VRA will be required (classification G.I.15 (z)).

You can find additional information in the 'EMA document on Quick Response (QR) codes'. This contains useful decision trees showing which option applies to you.