Frequently asked questions about parallel distribution

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This page lists questions about parallel distribution. The information is available as questions and answers, which the European Medicines Agency (EMA) revises as necessary.

Table of contents


General

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1. What is Parallel distribution?

Centrally authorised medicinal products ('CAPs') put on the market of one Member State can be marketed in any other Member State by a distributor, independently of the marketing-authorisation holder ('parallel distribution'). Parallel distribution (hereinafter also 'PD') pertains to all centrally authorised products and is checked by the European Medicines Agency (hereinafter 'the Agency').

Parallel import on the other hand concerns only nationally authorised products and is authorised by the national competent authority of the Member State of import based on the similarity to the product distributed in the Member State of destination by the marketing-authorisation holder (hereinafter 'MAH').

2. What are the procedures of parallel distribution?

The Agency fulfils its obligation to check the conditions of parallel distribution by means of four procedures.

Initial Notification

An initial notification is a parallel distributor’s notification to the Agency, informing of their intent to source, repackage and distribute a centrally authorised medicinal product from one or more Member States to one or more Member State(s). The Agency checks compliance of the particulars of this notification with the marketing authorisation and EU legislation on medicinal products and issues a PD notice when the check confirmed that for the medicinal product distributed in parallel, the conditions laid down in the EU legislation on medicinal products and in the marketing authorisation were observed at the time of issuance. For further information on how to submit an initial notification, please refer to the section 'Initial notification'.

Notification of Changes

A notification of changes provides the possibility for a parallel distributor to notify the Agency about the changes in the medicinal product.

There are two kinds of notifications of changes:

  • the mandatory safety update and
  • the optional notification of changes.

For further information please refer to the section on notification of changes/ bulk change/ annual update.

Bulk Change

A bulk change is a notification of changes for one or more changes that affect all of a parallel distributor’s medicinal products, at any point in time after the approval of the initial notification. The scopes that can apply to a bulk change are limited. For further information, please refer to the section on notification of changes/ bulk change/ annual update.

Annual Update

An annual update is an alternative (not a substitution) to the notification of changes. The purpose of the annual update is to combine all scopes of changes occurring within one year to one pharmaceutical form of a medicinal product with one Member State of destination in one application. It is aimed at maintaining an up to date database. For further information, please refer to the section on notification of changes/ bulk change/ annual update.

3. Are the Agency parallel distribution notification procedures mandatory?

Yes, since entry into force of Regulation (EC) No 726/2004 on 20 May 2004, notifications of parallel distribution of centrally authorised medicinal products have become mandatory throughout the EU.

Article 57(1)(o) of Regulation (EC) No 726/2004 of the European Parliament and the Council laying down EU procedures for the supervision of medicinal products and establishing the Agency determines the following task for the Agency:

'Checking that the conditions laid down in EU legislation on medicinal products and in the marketing authorisations are observed in the case of parallel distribution of medicinal products authorised in accordance with this Regulation'.

Moreover, Article 76 (4) of Directive 2001/83/EC confirms the applicability of a fee to be paid:

'In the case of medicinal products which have been granted an authorisation pursuant to Regulation (EC) No 726/2004, the distributor shall submit the notification in accordance with paragraph 3 of this Article to the marketing authorisation holder and the Agency. A fee shall be payable to the Agency for checking that the conditions laid down in Union legislation on medicinal products and in the marketing authorisations are observed.'

The obligation of notifying the Agency allows it to check compliance of the medicinal product to be distributed in parallel with the conditions laid down in the EU legislation on medicinal products and in the marketing authorisation. The outcome of the check is shared with the MAH who is responsible for the safety, efficacy and quality of the medicinal product and with national competent authorities so they can effectively monitor the market (batch identification, pharmacovigilance, etc.) and carry out post-marketing surveillance.

If the medicinal product is distributed in parallel, in the absence of the Agency’s check or despite the Agency’s letter of non-compliance, the national competent authorities may take regulatory actions regarding the said parallel distributor.

4. What is the parallel distribution notice?

The parallel distribution notice (“the PD notice”) is a document issued as a result of the Agency having conducted its check of the parallel distributor’s initial notification and the Agency having confirmed that for the medicinal product distributed in parallel the conditions laid down in the EU legislation on medicinal products and in the marketing authorisation were observed at the time of issuance.

Following the issuance of the PD notice, updates and changes shall be notified to the Agency by a notification of changes, a bulk change or an annual update. The Agency will issue the notice of changes, the notice of a bulk change, the notice of an annual update accordingly.

The notice of changes, the notice of a bulk change, the notice of an annual update confirm that for the medicinal product distributed in parallel the conditions laid down in EU legislation on medicinal products and in the marketing authorisation were observed at the time of issuance.

The PD notice, the notice of changes, the notice of a bulk change, and the notice of an annual update are cumulatively referred to as the Notices for PD.

5. What if a Notice for PD cannot be issued?

It may happen in any procedure (initial notification, notification of changes, bulk change and annual update) that the Agency’s check will establish that for a medicinal product the conditions for parallel distribution laid down in the EU legislation on medicinal products and in the marketing authorisation are not observed. In such a case the Agency will issue a letter of non-compliance.

The letter of non-compliance will be sent to the parallel distributor, to the MAH of the product concerned and to the national competent authorities ('NCAs') concerned. The letter confirms that for the medicinal product distributed in parallel the conditions laid down in the EU legislation on medicinal products and in the marketing authorisation were not observed at the time of issuance.

6. What is the public register of parallel distribution and what is its purpose?

The public register of PD notices (hereinafter also as 'the PD register') is a public register of the Agency’s most current list of medicinal products checked to be in compliance with the marketing authorisation and EU legislation.

Once the PD notice is issued, the Agency will record this fact in the PD register. The record will be removed when the letter of non-compliance regarding the particular product for the particular parallel distributor is issued or when the medicinal product is marked dormant. For further details see the question: 'What happens if the product is not distributed for the last 12 months' in the section 'Notification of changes / bulk changes / annual update'. Notification of changes /bulk changes/ annual update

If the medicinal product/parallel distributor does not appear in the PD register this means that either no PD notice was issued at all or subsequently to the issuance of the PD notice, the medicinal product was marked dormant or the letter of non-compliance was issued because for the medicinal product distributed in parallel the conditions laid down in EU legislation on medicinal products and in the marketing authorisation were not observed.

7. What are the post-PD notice obligations of a parallel distributor?

Updates

The medicinal product distributed in parallel must always be in compliance with the latest version of the marketing authorisation and EU legislation on medicinal products. This may require introducing changes to the labelling and the package leaflet.

Changes concerning the medicinal product distributed in parallel or concerning the parallel distributor have to be checked by the Agency. This is done in the course of the post-PD notice procedures which comprise: notification of changes, bulk change, and annual update.

Quality Defects and Rapid Alerts

If a parallel distributor identifies a quality defect of the product when sourcing it, or as a result of subsequent handling in the distribution chain, the parallel distributor is accountable and must report this to the Agency.

For further information regarding the procedure of reporting, please see the section on Post- PD notice guidance.

Pharmacovigilance

According to Title IX of Directive 2001/83/EC, the responsibility for pharmacovigilance lies with the Member States and the marketing-authorisation holder. The Agency does not request any information regarding pharmacovigilance or the responsible person for pharmacovigilance from the parallel distributor during the notification procedure. For more information on the Article 57 Database, please see the legal notice.

Should the parallel distributor receive a notification of an adverse drug reaction from a patient, a doctor or any other source, the parallel distributor should inform this person that the adverse drug reactions should be reported directly to the marketing-authorisation holder of the medicinal product. The parallel distributor should do the same immediately.

8. Are parallel distributors allowed to open the packaging? Can the medicinal product distributed in parallel be repackaged?

In principle, the only changes to the medicinal product which can be required in order to allow parallel distribution are changes in the language of the labelling and package leaflet to comply with requirements of legislation on medicinal products. Thus, in general, repackaging shall not be allowed.

However, replacing the packaging of a medicinal product is sometimes objectively necessary if, without such repackaging, effective access to the market concerned, or to a substantial part of that market, would be hindered. The necessity of repackaging must be justified by the parallel distributor in the course of a notification procedure.

The possibility to repackage medicinal products is thoroughly assessed on a case-by-case basis, to ensure compliance with the marketing authorisation of the medicinal product and EU legislation on medicinal products for the safety of patients. In particular, the repackaging cannot adversely affect the original condition of the product. The concept of adverse effects on the original condition of the products refers to the condition of the product inside the packaging. It is accepted that the condition of the product is not adversely affected when repackaging affects only the external layer, leaving the inner packaging intact.

The removal of blister packs from their original external packaging and their insertion with one or more original packages into new external packaging, or their insertion in another original package, the fixing of self-stick labels on original external packaging or blister packs, or the addition to the packaging of new user instructions or information is considered as an activity which shall not affect the condition of the medicinal product inside the packaging.

9. Who assesses the concept of the effective access to the market?

Some changes to the packaging (e.g. repackaging) of the medicinal product may be allowed if this is necessary for the medicinal product distributed in parallel to have effective access to the market.

It is for the Agency to check the compliance of the medicinal product distributed in parallel with the latest version of marketing authorisation and the EU legislation on medicinal products. To this end, it is for the Agency to assess if the changes to the packaging are necessary for the medicinal product to have effective access to the market and if the changes are compliant with the marketing authorisation and the legislation on medicinal products.

When conducting its assessment the Agency takes into account the parallel distributor’s justification and consults concerned Member States if necessary.

10. Are any deviations/differences from the text of the latest marketing authorisation allowed?

The Agency checks if the package leaflet and the labelling (inner and outer) of the medicinal product are in compliance with the EU legislation on medicinal products and with the marketing authorisation in the language of the Member State of destination. No deviations/differences are allowed because in principle the medicinal product distributed in parallel shall be identical to the medicinal product distributed by the MAH. However, some minor deviations are allowed due to parallel distribution specifics. For further details please refer to the exceptions as listed in the section ‘What are additional requirements reflecting that the product is distributed in parallel?’.

11. Can centrally authorised products be rebranded?

No, centrally authorised medicinal products cannot be rebranded. The marketing authorisation for centrally authorised products is valid in all Member States of the European Union and the only changes permitted for parallel distributed products are, in general, the changes in the language of the labelling and package leaflet.

12. Can centrally authorised products be sourced from Norway, Iceland and Liechtenstein?

Yes, the principles laid down in section D of European Commission Communication 98/C 229/03 on the Community marketing-authorisation procedures for medicinal products apply. The Agency notification procedures for parallel distribution will also apply for parallel distribution from Iceland, Norway and Liechtenstein, provided the products have been previously harmonised with the Union marketing authorisation. A parallel distributor can therefore source batches of a centrally authorised product in Norway, Iceland and Liechtenstein for parallel distribution in one or more EU Member States.

13. Is it possible to source a product from one Member State and parallel distribute it in the same Member State?

As parallel distribution is the distribution across European borders, sourcing a medicinal product from and distributing it to the same Member State market does not constitute parallel distribution.

14. Does the ‘specific mechanism’ apply to parallel distribution?

The specific mechanism applies to parallel distribution. Annex IV (2) of the Act of Accession signed on 16 April 2003 introduced a mandatory notification scheme through the specific mechanism, which now extends to Bulgaria and Romania as well as Croatia:

'With regard to the Czech Republic, Estonia, Latvia, Lithuania, Hungary, Poland, Slovenia or Slovakia, the holder or beneficiary of a patent or supplementary protection certificate for a pharmaceutical product filed in a Member State at a time when such protection could not be obtained in one of the above-mentioned new Member states for that product, may rely on the rights granted by that patent or supplementary protection certificate in order to prevent the import and marketing of that product in the Member State or States where the product in question enjoys patent protection or supplementary protection, even if the product was put on the market in that new Member State for the first time by him or with his consent.

Any person intending to import or market a pharmaceutical product covered by the above paragraph in a Member State where the product enjoys a patent or supplementary protection shall demonstrate to the competent authorities in the application regarding that import that one month’s prior notification has been given to the holder or beneficiary of such protection.'

The legal responsibility for enforcing intellectual property rights remains with the patent or supplementary protection certificate holder.

When submitting an initial notification or an annual update/notification of changes to the Agency, parallel distributors are required to specify the Member State(s) of origin and of destination of the medicinal product they intend to distribute parallel and to specify whether the specific mechanism applies to the concerned notification. Parallel distributors are also requested to confirm that the patent holder or beneficiary has been given one month’s advance notice in their application when the specific mechanism applies, by attaching a signed prior letter to the notification.

15. Can a centrally authorised product be parallel distributed in a Member State where the marketing-authorisation holder has not yet placed the relevant product presentation on the national market concerned?

When a medicinal product has been authorised at EU level, the marketing-authorisation is valid throughout the EU. A parallel distributor may therefore distribute a particular presentation of a centrally authorised product on the market after obtaining a PD notice from the Agency even if the MAH has not yet placed this presentation on the market in this Member State.

16. Is the Agency involved in any trademark issues?

No, the Agency is not involved in any trademark issues and only checks the compliance of the medicinal product distributed in parallel with the terms of the EU marketing-authorisation of the concerned centrally authorised product and EU legislation on medicinal products.

It is up to the trademark owner to check if the repacked product does not damage the reputation of the trademark, while the Agency is responsible for checking compliance of the submitted specimens with the terms of the EU marketing-authorisation and EU legislation on medicinal products.

The Agency does not take decisions or provide guidance on the use of registered trademark symbols.

17. What are the responsibilities of a parallel distributor regarding biologics (e.g. vaccines and blood products)?

Pursuant to Article 114 of Directive 2001/83/EC, Member States may impose additional requirements regarding live vaccines, immunological medicinal products and blood or plasma derived products.Parallel distributors are, in general, obliged to notify the national authority of the Member State of destination responsible for the parallel distribution of products which are subject to official control authority batch release such as vaccines or blood products.

Additionally, the Agency will send a copy of the Notices for PD and letters of non-compliance for parallel distribution of a vaccine or blood product to the relevant national competent authority of the Member State of destination.

18. Are a wholesale authorisation and/or a re-packager’s manufacturing authorisation needed in order to allow parallel distribution?

Yes, a wholesale authorisation and/or a re-packager’s manufacturing authorisation is needed in order to allow parallel distribution.

All parties (parallel distributor and re-packager) must hold the appropriate authorisations for the activities in which they are engaged, i.e. a wholesale distribution authorisation and/or manufacturing authorisation. Repackaging activities can be carried out either by the parallel distributor or another company, provided these companies have valid manufacturing authorisations. All authorisations should be available on the EudraGMDP website.

A copy of an up-to-date and complete (with attachments) original authorisation or a EudraGMDP reference should be submitted only with the first initial parallel distribution notification. It is also recommended to attach an English official translation of the authorisation(s) to facilitate the review and validation by the Agency when a copy of a paper authorisation is submitted. For more information please see, EudraGMDP website.

19. Can a parallel distributor use more than one re-packager?

Yes, parallel distributors are allowed to identify more than one re-packager in their parallel distribution notification. The EudraGMP reference number must be provided with every re-packager added, alternatively the copy of the manufacturing authorisation should be provided.

On the proposed outer labelling, the parallel distributor can only state one re-packager (and optionally the address), namely the one who is responsible for particular batch release. Only one colour copy with one re-packager has to be provided as an example.

20. Can the PD notice be transferred?

No, transferring a PD notice from one company to another is not possible.

Article 76 of Directive 2001/83/EC imposes the individual obligation on the distributor who intends to import a medicinal product from another Member State to submit the notification to the marketing authorisation holder and the Agency in case of medicinal products which have been granted an authorisation pursuant to Regulation (EC) No 726/2004.

However, if as a result of a merger/acquisition the parallel distributor is dissolved or if it changes the legal form, there is an assumption of continuity of the legal entity. Therefore, change of name and address is sufficient to reflect the said change. In these situations, a notification of a bulk change would need to be submitted. To this effect, the parallel distributor must provide a statement confirming that it has taken over all rights and obligations of the previous parallel distributor.

Initial notification

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1. How to obtain an EMA parallel distribution customer number?

To apply for an EMA customer account for parallel distribution, please complete the below form and submit it as a Microsoft Word (.doc) with your first initial application for parallel distribution.

Customer form

Please submit this form only once, with your first initial notification. Once you have been issued a customer number, this should always be inserted in the relevant field in the forms.

2. What is Eudralink and how can I apply for a Eudralink account?

Eudralink is a secure file transfer system used by the European medicines regulatory network to exchange information for regulatory purposes. It has been designed to enable files to be sent securely over the internet via a user-friendly web interface.

Eudralink users can create packages containing one or more files with a maximum size of 40 megabytes per file to be collected by specified recipients. For security purposes, packages are encrypted when in storage and in transit using 128bit strong encryption.

Eudralink accounts are supplied on a 'one-per-person' basis and should not be shared between users. Parallel distributors with more than one person involved in the notification process should request individual accounts for each person.

To apply for a Eudralink account, please complete the below form and send it as a Microsoft Word document (.doc) to a new e-mail address: eudralink@ema.europa.eu.

Service desk staff will contact the parallel distributor once the Eudralink account request has been approved. Please note that the first 3 sections ('personal information', 'work information' and 'motivation') are mandatory, however the last section (information on the European Medicines Agency or MS contact point (PTL) for account request if available) may be left blank if this information is not available.

Notes

  • Eudralink accounts are only available to users who have access to business e-mail accounts in the medical and pharmaceutical industries. Web-based e-mail accounts such as Yahoo!, Hotmail, and Gmail etc. are not acceptable.
  • If you already have a Eudralink account and are changing companies or you no longer require your Eudralink account, please contact Service desk staff at the Agency so they can keep your details up-to-date or delete your account.
  • The Eudralink request form is a legal document. By requesting a Eudralink account, you are agreeing that all the information you have provided is current and correct.
3. Which mailboxes are to be used for submitting initial notifications, annual updates/notifications of changes or general enquiries?

For general enquiries on parallel distribution: paralleldistribution@ema.europa.eu.

For initial notifications: pd_esubmission@ema.europa.eu.

For annual updates/notifications of changes: pd_esubmission_changes@ema.europa.eu.

Please always use only the relevant mailbox.

4. How to apply for the PD notice?

Step 1 - Request a Eudralink account in order to be able to send an initial notification via a secure platform (see ‘What is Eudralink and how can I apply for a Eudralink account?’).

Step 2 - Request a customer account number (see 2.1.   How to obtain an EMA parallel distribution customer number?)

Step 3 - Compile documentation including the below documents:

  • a scan of the latest manufacturing authorisation of the parallel distributor and/or re-packager (ONLY with the FIRST application) or a reference to EudraGMDP website;
  • a scan of the latest wholesale distribution authorisation of the parallel distributor (ONLY with the FIRST application) or a reference to EudraGMDP;
  • a scan of the signed cover letter clearly indicating the name of the medicinal product, the strength, the pharmaceutical form, EU number and the pack-size and any other relevant information;
  • a completed electronic version of the initial notification form (notification of parallel distribution of a centrally authorised medicinal product) from the official contact person - signature is not required;
  • an editable format of the package leaflet (doc, pdf) in the language of the Member State of destination in compliance with the latest version of the EU marketing-authorisation;
  • a colour scan of all sides of the re-labelled and/or re-packed outer packaging, as well as the re- labelled inner packaging, as they will be marketed in the Member State of destination, clearly showing the braille text label if required according to the marketing-authorisation;

Note: When submitting the first initial notification for parallel distribution of a centrally authorised product, the parallel distributor will be requested to provide the Agency with images of the finalised product. Mock-ups do not suffice in this instance.

The Agency reserves the right to request images of the finalised product at any time.

  • a signed prior notice letter in case the specific mechanism is applicable.

Step 4 - Send documentation via Eudralink to: pd_esubmission@ema.europa.eu.

It is strongly recommended that new parallel distributors submit only one notification when applying for a notice for parallel distribution for the first time and wait for the outcome of the parallel distribution notification check in order to avoid the repetition of errors when submitting subsequent notifications.

Should a parallel distributor submit a package by mistake or discover an error in the submitted package, it should be removed on the same day. The fees will be payable upon confirmation of receipt of the notification.

Step 5 - If all supporting documentation is satisfactory, the Agency will finalise the parallel distribution notification check and issue a PD notice. If necessary, the parallel distributor will be contacted by a parallel distribution assessor. Please note that all communication regarding a particular application should be directed at the parallel distribution assessor who requested the follow-up information.

In case of general queries regarding parallel distribution, please send an e-mail to paralleldistribution@europa.ema.eu.

5. How do I submit a Eudralink package?

Please note that a separate Eudralink message is required for each initial notification or annual update or notification of changes.

The subject of Eudralink packages should include the following information:

  • 'Date in ICH format (i.e. YYYY.MM.DD)' 'PD Name'_'Product Name'_' last 3 digits of the EU number(s)'_'Submission Type'_'Sequence number'

PD’s name (a short name is acceptable)

Product name (only one product and strength per Eudralink message)

Please note that it is possible to combine different pack sizes of the same product and strength in one Eudralink message, but separate messages are required for different strengths of the same product and for different products. For example, the following two pack sizes:

Stalevo (EU/1/03/260/003) 50 mg / 12.5 mg / 200 mg Film-coated tablet (100 tablets) and Stalevo (EU/1/03/260/004) 50 mg / 12.5 mg / 200 mg Film-coated tablet (250 tablets)

E.g. 2010.07.06 ABCD_Stalevo_003_004_initial_00

An exception to this is the annual update. For more information please see, section ‘notifications of changes / bulk changes / annual update’.

The body of the message is free and may contain, for example, information on the different attachments. However, we recommend not including too much information in this section. All relevant information should be included in the cover letter.

The Eudralink message must be addressed to: pd_esubmission@ema.europa.eu for all initial notifications and to: pd_esubmission_changes@ema.europa.eu for annual updates/notifications of changes. The validity of the Eudralink message must have the maximum expiry period of 90 days and the option 'The recipient(s) must have a Eudralink account to access the package' must be selected.

A Package Tracking facility allows Eudralink users to monitor when their package has been collected. This enables parallel distributors to acknowledge receipt of information.

Any subsequent document regarding an on-going initial notification, annual update or notification of changes should be submitted via e-mail or Eudralink to the same parallel distribution assessor handling the notification, unless the Agency has informed the parallel distributor about a change in responsibility. The subject of the e-mail or Eudralink message should follow the instructions mentioned above (i.e. PD name_Product Name_EU Number_02).

General enquiries on the status of a particular notification can be sent to the parallel distribution assessor handling the notification or to: paralleldistribution@ema.europa.eu.

6. What file formats are acceptable?

All documentation should be submitted using file formats that facilitate the assessment of the file on screen. If the type of file you plan to upload or send via e-mail is not included in the list below, please convert the file to an acceptable file type.

Data

xls (Microsoft Excel Spreadsheet)

Image

bmp (Bitmap Image)

 

gif (Graphics Interchange Format)

 

jpg (Joint Photographic Experts Group)

 

pdf (Portable Document Format)

 

tif (Tagged Image File Format)

 

Text

doc (Microsoft Word Document)

 

docx (Microsoft Word Open XML Document)

 

pdf (Portable Document Format)

 

Compressed

zip (Zipped File)

PDF documents submitted as scans should be scanned at resolutions that will ensure the pages are legible both on the computer screen and when printed. Normally 300 dpi gives good results without compromising file size for text. Parallel distributors should ensure that the quality of the renditions is adequate for regulatory review.

7. How to name each file?

Standardisation of the electronic file names is necessary for easy identification of the content and filing in the Agency’s document system. The proposed naming is the following:

'Date in ICH format (i.e. YYYY.MM.DD)' 'PD name'_'Product Name'_'lastthree digits of the EU number'_'Subject'

It is possible to use short names for PD name, provided that it is not ambiguous and/or confusing and it is agreed with the Agency. For example: 'ABCD' instead of 'ABCD Pharma'.

Possible subjects:

  • 'cover' for cover letters;
  • 'form' for notification forms;
  • 'leaflet' for package leaflets;
  • 'labelling' if all labelling (inner and outer) in the same file;
  • 'outer' if outer labelling only in the file;
  • 'inner' if inner labelling only in the file;
  • 'braille' for braille text labels;
  • 'manufacturer' for the manufacturing authorisation of the parallel distributor or the re-packager;
  • 'wholesale' for the wholesale distribution authorisation of the parallel distributor;
  • 'prior' for the prior notice letter in the frame work of the specific mechanism.

e.g. 2010.07.06 ABCD_Stalevo_003 _Outer

File names should not exceed 230 characters to avoid technical problems. File names should not contain characters which are known to cause problems. Files themselves must not be password protected or include security settings that may interfere with the process of handling by the reviewers.

8. Are electronic signatures accepted?

Although electronic signatures are currently accepted in the EU as being legally equivalent to handwritten signatures (Directive 1999/93/EC), the Agency does not currently have a system in place for receiving electronic signatures and therefore requires that the cover letter is signed, scanned and included in the documentation package. The cover letter and the 1-month prior letter sent to the Marketing-authorisation holder in the case of the specific mechanism being applicable will be the only documents requiring a signature. There is no need to send these by post.

9. How many initial notifications can be submitted per medicinal product?

A separate notification must be submitted for each EU-number and for one Member State of destination having one or more official languages, or for several Member States of destination having the same official language.

10. Where to find the latest published annex/EU marketing authorisation?

To check the latest version of the annex of the centrally authorised product via the Agency website please visit the European Public Assessment Report (EPAR) section.

To check the latest version of the annex via the European Commission registry on medicinal products, please visit the Community Register.

Note that there might be a discrepancy between these websites; this might be due to one of the websites not yet having been updated. In that case you should use annex with the later publishing date.

In case of doubt please double-check with the parallel distribution team by sending an e-mail to paralleldistribution@ema.europa.eu.

On a monthly basis the parallel distribution team will provide you with a SIAMED extract. SIAMED is the Agency’s internal database for recording all data with regards to centralised products and provides the most accurate information with regards to the latest version of the annex. This list should be used in combination with both above named websites when looking up the latest version of the annex.

11. How to proceed if sourcing a product from a country where the language is the same as the language in the Member State of destination?

If a parallel distributor sources a product from a country where the official language is the same as the language in the Member State of destination (e.g. Ireland, Malta and UK or Austria and Germany) the parallel distributor is still required to provide complete labelling for the product. The European Court of Justice has defined “repackaging” as including operations such as “removal of blister packs from the original external packaging and their insertion into new external packaging” or “addition to the packaging of new user instructions or information or the fixing of self-stick labels’’. If a parallel distributor is planning to add even a small labelling on the outer carton (e.g. with the name of the parallel distributor), this is still considered ‘repackaging’ and needs to be performed by a company that holds a manufacturing authorisation.

In such instances, the notification form or signed cover letter should also clearly state for each country involved, that ‘’Products sourced in Member State A will not be parallel distributed in Member State A.’’

Labelling

Example: If a parallel distributor sources a product in the United Kingdom with the intention to distribute in parallel it in Ireland, the relabelling activity could be limited to adding the details of the parallel distributor, re-packager, manufacturer responsible for batch release, and the ‘blue box’ in case the product information is already in compliance with the latest version of the annex. If not, the missing additional information in the language of the Member State of destination should be added to the outer labelling as well. In the instance that Member States of origin with other languages are indicated in the form, the parallel distributor will need to provide full sets of labelling examples to the product sourced in a different language. Parallel distributors must ensure that only the Member State(s) where the product will be placed on the market are mentioned inside the ‘blue box’.

Package leaflet

Example: If a product is sourced in the United Kingdom and the package leaflet is in compliance with the latest version of the annex and country specific requirements of the member state of destination, there is no need to exchange the package leaflet as mentioning the parallel distributor’s details and the re-packager in the leaflet are not mandatory. In the instance that Member States of origin with other languages are indicated in the form, the parallel distributor will need to provide package leaflet examples for the product sourced in a different language.

Parallel distribution notification check

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1. What is the timeframe for the check?

The Agency finalises the check within 60 days after confirming the receipt of the notification. It will then issue either the appropriate Notice for PD or the letter of non-compliance. 60 days comprises 35 days for the Agency’s assessment and 25 days for possible clock-stops.

The Agency conducts its check within 35 days from the day of confirmation of the receipt of the notification. For the initial notifications the confirmation will be sent within 1 working day following the receipt. Once the conditions laid down in the EU legislation on medicinal products and in the marketing authorisation are observed, the Notice for PD will be issued.

If there is any obstacle for the issuance of the Notice for PD, the parallel distributor will be informed thereof and the time-limit of 35 days shall be suspended until the parallel distributor replies to the Agency’s comments. The parallel distributor may be asked to supplement or change the parallel distributor details, change or supplement the labelling or package leaflet or to provide clarification regarding the application.

The clock-stop may be granted several times. The total time of clock-stop may not exceed 25 days. The parallel distributor will be reminded twice of the time-frame. First, after he uses 10 days of the clock-stop and second, if he has only 5 days of clock-stop remaining. If the parallel distributor fails to comply with he Agency’s comments within 25 days of clock-stop, the check will be finalised and the letter of non-compliance will be issued.

The parallel distributor should provide a response directly to the assessor who requested it and should clearly indicate the subject of the e-mail as follows:

'Date in ICH format (e.g. YYYY.MM.DD)' 'parallel distributor’s name'_'Product Name'_'last 3 digits of the EU number(s)'_'Subject' (see section 'initial notification').

The time-limit is common for every procedure.

2. Are there any exceptions allowed to the timeframe?

The extension of the time-frame is allowed only exceptionally and is possible only in the situations in which despite the good-will of the parallel distributor additional time is necessary to finalise the check. The exception to the timeframe has to be applied for by the parallel distributor and be thoroughly justified.

The extension may be granted in the following cases:

  1. The variation of the marketing authorisation during the procedure;
  2. The need to have a one month period elapsed in case of a specific mechanism;

The need to wait for manufacturer’s mock-ups which for technical reasons is beyond the control of the parallel distributor.

3. Is it allowed to resize or create bundle packs?

It is not possible to bundle two units of a presentations of a product so as to create a new presentation of a different size.

Bundle packs can only be created when bundle packs are explicitly listed in the packaging description of the marketing authorisation.

This needs to be distinguished from multipacks, which per marketing authorisation are presentations that consist of multiple units of size x, ‘bundled together’ to create size y.

Presentations that consist of one unit of size x can be used to create size y (resizing).

4. What is the difference between a mock-up and a colour copy?

A mock-up is a copy of the label or flat artwork design in full colour, providing a replica of both the outer and inner packaging and labelling text of the medicinal product. It is generally referred to as a paper copy or computer generated version.

A colour copy is a digital scan, a digital photograph or a colour photocopy of the (repackaged) sales presentation of the medicinal product.

The printed package leaflet should be representative (format and content) of the sale presentation.

Note: Please always submit a mock-up or colour copy of the outer and inner packaging and an editable version of the package leaflet together with the notification form. The mock-up, colour copies and the editable package leaflet version have to be clear and easily readable. Without these documents, the notification cannot be validated. Please ensure that the labelling and package leaflet are in compliance with the latest version of the annex of the EU marketing authorisation.

In addition please be aware, that the responsible assessor may request images of the final product or, in exceptional circumstances, a physical sample at any point.

5. What to do if the marketing-authorisation holder or the manufacturer of a particular centrally authorised product has changed?

If the MAH (or the MAH’s address or name) or manufacturer of a particular centrally authorised product has changed, it is recommended that parallel distributors always use the latest version of the Annex when releasing a product. In case there are changes in the manufacturer’s details, parallel distributors must always use the latest version of the Annex but indicate the manufacturer responsible for the particular batch release as listed in the sourced package leaflet.

The parallel distributor may however distribute these products which have already been labelled in compliance with the previous Annex.

6. What to do if the excipients or devices used have changed with new batches?

If the medicinal product has been sourced from an old batch and some of the excipients have changed, the parallel distributor needs to use the most recent published annex, but mention the excipients or devices as listed in the previous annex.

7. What are additional requirements reflecting that the product is distributed in parallel?

The following are additional mandatory requirements for the outer labelling, even if they are not mentioned in the annex:

  • manufacturer responsible for batch release (as mentioned in the original package leaflet of the concerned batch);
  • the words ‘parallel distributor/parallel distributed by’ (followed by the name and optionally the address) or the words ‘re-packager/repackaged by’ (followed by the name and optionally the address);
  • braille text (if mentioned in section 16 of the annex);
  • 'blue box' (in accordance with national regulations of the Member State of destination).

Optional terms

  • <Product X> is a trademark of <Company Y>;
  • internal reference number of the parallel distributor (for further information, please see, section 'Parallel distribution notification check').

The following terms are not allowed to appear on the outer labelling:

  • 'procured from within the EU';
  • 'imported by';
  • more than one manufacturer responsible for batch release;
  • any other text which is not part of the latest version of the annex (unless justified).

The following terms are allowed to appear on the inner labelling but are not mandatory:

  • 'parallel distributor/parallel distributed by:' (followed by the name and optionally the address);

or

  • 're-packager/repackaged by:' (followed by the name and optionally the address);
  • <Product X> is a trademark of <Company Y>;
  • internal reference number of the parallel distributor (for further information please see, section 'Parallel distribution notification check').

Mandatory terms to appear in the package leaflet:

  • manufacturer responsible for batch release (same as the one on the outer labelling);
  • local representatives if they are present in the annex.

Exceptions

Minor changes are permitted to be introduced by the parallel distributor in the text of the labelling/package leaflet in the following situations and only with the agreement of an assessor:

  • when the composition of a medicinal product changes the parallel distributor must ensure that the composition mentioned in the leaflet/labelling of the parallel distributed pack corresponds with the actual composition of the pack. The parallel distributor is allowed to modify the text referring to the composition and use the relevant information from the previous annex. All other medical information should correspond to the latest version of the annex;
  • when the term 'Sealed pack' is mentioned in the annex there are two options:
  1. if a parallel distributor opens a sealed pack to re-label the box and to replace the package leaflet in such a way that after re-labelling the patient will still receive an integral box with the original seal unbroken, then the sentence 'Sealed pack. Do not use if box has been opened.' should be included on the outer labelling;
  2. if a parallel distributor breaks the seal in order to re-label the box and to replace the package leaflet and then seals the box with a clear seal, the phrase 'Sealed pack. Do not use if box has been opened.' should be removed and replaced with ‘Sealed pack has been opened for the purpose of parallel distribution'.
8. Can several languages be combined in one pack?

The EU pharmaceutical legislation mentions in Article 63 (1) of Directive 2001/83/EC that all text shall appear in the official language(s) of the Member States where the product is placed on the market.

The labelling and the package leaflet should be in compliance with the text of the EU marketing authorisation for the concerned medicinal product in all official languages.

In the case of multilingual Member States of destination (i.e. Belgium, Finland, etc.), the parallel distributor must combine all languages of that particular country in the package leaflet and on the labelling.

A parallel distributor can create a multilingual pack provided that all particulars required by the marketing authorisation appear in all languages concerned. The outer carton should then contain separate blue boxes for each member state of destination.

9. Is it allowed to add internal codes to the labelling?

The parallel distributor is allowed to add an additional re-pack batch number or an internal code, provided that they are not a part of a core text. The additional re-pack batch number can be a different number or it can be a derivative of the original batch number with an added prefix or suffix.

10. What are the general requirements for the braille text labelling?

The guideline on the readability of the labelling and package leaflet of medicinal products for human use as prepared by the European Commission (2009 D/869) sets out advice on the presentation of the content of the labelling and package leaflet and on the design and layout concepts meant to aid the production of high quality information.

The guideline clearly and unequivocally sets out how the requirements for braille text can be met.

As mentioned in the guidance concerning the braille requirements for labelling and the package leaflet from the European Commission, these requirements are applicable to parallel distributors.

Further guidance on braille text can be found on national websites as well as:

When submitting specimens or ‘mock-ups’, parallel distributors are recommended to ensure, that the braille text presentation is submitted in the language of the Member State of destination, in compliance with the annex.

When the original braille text matches the braille text of the country of destination, the original braille text can be maintained provided that legibility and readability criteria apply.

According to Article 56a of Directive 2001/83/EC, the name of the medicinal product must be expressed in braille. This has to be in the language of the Member State of destination. As further clarified by the European Commission in above mentioned guidance the name should be followed by its strength, unless the medicinal product was only authorised in a single strength.

The Agency strongly advises parallel distributors to affix the new braille text on a different part of the outer packaging, and not on top of the original one.

The braille text is not mandatory on the immediate packaging (such as blisters, ampoules and bottles) unless required by the marketing authorisation.

The colour copy should make the braille text visible and readable. New braille text presentations must be submitted along with the indication where the braille text will be affixed on the outer packaging.

If the braille text is added on a separate label, a copy of this label should be added to the colour copy of the labelling or the documents submitted with the notification.

11. What are the special requirements for unit dose blisters?

As a general note, when labelling unit dose perforated/peelable blisters, each segment of a perforated blister must be re-labelled individually following the same approach as that of the marketing-authorisation holder.

Please note that parallel distributors are not allowed to create a unit dose presentation from a non- unit dose presentation.

12. Is it allowed to cut blisters?

The cutting of blisters is not recommended by the Agency but may occasionally be permitted on a case-by-case basis, provided that it does not affect the original condition of the product and the proposals from the parallel distributor are in compliance with the conditions of the marketing authorisation. The assessment takes into account the necessity for the effective access to the market.

The parallel distributor should provide a valid justification for cutting blisters and a decision on whether this is acceptable will be made by the Agency.

13. How to re-label sterile and foil pack products?

As the original condition of the product may be altered by the opening of a sealed foil pack, a blister or a tray, when re-labelling the blister, syringe, cartridge or other primary packaging, the Agency strongly recommends:

  • not to open the tray to re-label the syringe but instead to re-label the tray with all information required for the syringe and the tray preventing any possible contamination of the syringe or of the medicine itself;
  • not to open the aluminium wrapper/foil as the foil provides protection and is important for the maintenance of the shelf life of these products.
14. How many manufacturers are allowed in the package leaflet and on the outer labelling?

Article 59 (f) (vii) of Directive 2001/83/ECrequires that the marketing-authorisation holder should always state only one manufacturer responsible for the batch release in the original package leaflet.

When more than one manufacturer is indicated in the sourced original package leaflet, the parallel distributor has to contact the marketing-authorisation holder to obtain information on the manufacturer responsible for the particular batch release. When the parallel distributor sources product that lists more than one manufacturer in the original package leaflet, it is essential to notify the Agency about this and the Agency will liaise with the marketing-authorisation holder in order to rectify this.

Please note that only one manufacturer shall be mentioned on the outer label, namely the manufacturer responsible for the release of the concerned batch as mentioned in the original leaflet. The manufacturer on the outer label should always correspond to the one in the package leaflet.

15. What is the recommended font-size of the labelling and the package leaflet?

The guideline on the readability of the labelling and package leaflet of medicinal products for human use gives recommendations on the font size of the text for the outer and inner labelling and the patient leaflet to ensure their legibility.

Concerning the package leaflet, the guideline states that ‘The type size should be as large as possible to aid readers. A type size of 9 points, as measured in font 'times new roman', not narrowed, should be considered as a minimum.

With regards to the labelling, the guideline states that 'The particulars appearing on the label of all medicinal products should be printed in characters of at least 7 points (or of a size where the lower case 'x' is at least 1.4 mm in height), ...'.

16. What are the requirements for the 'blue box'?

The 'blue box' is mandatory on the outer labelling of each centrally authorised product as well as each parallel distributed product. The information required to appear inside the 'blue box' is specific to each Member State. Each 'blue box' must state the name of the Member State of destination and the information required by the Member State of destination as described in the guideline on the packaging information of medicinal products for human use authorised by the EU.

The original ‘blue box’ should be completely covered. In principle the border of the blue box should be blue.

According to Article 57 of Directive 2001/83/EC, a Member State may ask for additional information to appear on the packaging concerning identification and authenticity of the product, the legal category for supply and the price. In addition, Article 57 of Directive 2001/83/EC states that Member States shall observe the detailed guidance referred to in Article 65 of Directive 2001/83/EC when applying Article 57 with regard to centrally authorised medicinal products, such as the guideline on the packaging information of medicinal products for human use authorised by the EU. It has been prepared by the European Commission in agreement with the Member States and the parties concerned in order to describe how provisions of Directive 2001/83/EC apply, including the provisions in Article 57 of Directive 2001/83/EC.

17. Who receives Notices for PD and letters of non-compliance?

Notices for PD and letters of non-compliance are sent to the parallel distributor, to the MAH and to the national competent authorities in the Member State of destination and in the Member State where the parallel distributor is registered. For a vaccine or a medicinal product derived from human blood/plasma a Notice for PD and letter of non-compliance will also be sent to the national competent authority in the Member State of destination responsible for the supervision of vaccines and medicinal products derived from human blood/plasma.

Post - PD notice guidance

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1. What is the validity of the notice for parallel distribution and can it be revoked or annulled?

The PD notice is a document confirming that at the time of issuance, for the medicinal product distributed in parallel the conditions laid down in EU legislation on medicinal products and in the marketing authorisation were observed. If it is established that the medicinal product distributed in parallel is no longer compliant with the latest version of the marketing authorisation or with the EU legislation on medicinal products a letter of non-compliance will be issued for this product.

The Agency keeps publicly available the register of the PD notices issued which were not followed by the issuance of a letter of non-compliance or not marked dormant. Thus, the PD register represents the Agency’s most current list of medicinal products checked to be in compliance with the marketing authorisation and EU legislation.

In exceptional situations the PD notice may be annulled. The annulment of the PD notice may take place if the PD notice was issued due to an error or based on information which subsequently turned out to be incorrect. In such a case, the PD notice will be removed from the register and the MAH, NCAs and the parallel distributor will be informed thereof.

2. Can a centrally authorised medicinal product continue to be distributed in parallel if the marketing authorisation is suspended, revoked or withdrawn?

The medicinal product distributed in parallel is covered by the central marketing authorisation. As a consequence, the scope and validity of the marketing authorisation determine the situation of the medicinal product.

In case of a revoked, withdrawn or suspended marketing authorisation, no further batches can be released into the supply chain but the batches in the distribution chain can be used except in case of a recall.

3. Can the Agency request the national competent authorities to perform an inspection of a parallel distributor?

Where considered necessary, the Agency shall inform the national competent authorities of any issues or non-compliance that have been brought to the Agency’s attention which may trigger an inspection, in accordance with Article 111 of Directive 2001/83/EC.

The responsibility for any further action remains within the remit of the national competent authorities of the respective Member State(s).

4. What are the parallel distributors’ responsibilities regarding quality defects?

If a parallel distributor identifies a quality defect of the product when sourcing it, or as a result of subsequent handling in the distribution chain, the parallel distributor is accountable and must report this to their national competent authority as well as the Agency.

  1. A parallel distributor can make changes to the packaging materials of a product only if they hold a manufacturing authorisation issued by the relevant national competent authority. They are bound by the provisions of that authorisation, which include compliance with the principles and guidelines of good manufacturing practice (GMP) that are laid down in Directives 2003/94/EC and 91/412/EEC, for human and veterinary products respectively.

According to Article 13 of Directive 2003/94/EC, manufacturers are required to have a system for recording and reviewing complaints and for effective recall. A manufacturer is obliged to inform the national competent authority of any defect they have become aware of that might result in a recall or abnormal restriction in supply. This applies equally to parallel distributors, as provided for by Article 80 of Directive 2001/83/EC. The national competent authority will assist the parallel distributor in the recall process and will initiate the rapid alert system accordingly. A parallel distributor should ensure that the marketing-authorisation holder is informed of any recall initiated by the parallel distributor.

  1. Parallel distributors must only source products from companies which have a valid wholesale distribution authorisation in the Member State where they are located. The supplier is consequently obliged to inform the parallel distributor of any recall activities that might involve products supplied to the parallel distributor within the supply chain. Such notifications must be handled within the parallel distributor’s GMP/GDP (good manufacturing/distribution practices) system to confirm whether the affected product was actually received, to trace its utilisation and to initiate recall procedures as necessary, including contacting the local competent authority.

When a parallel distributor encounters a quality defect or has any suspicion about the sourced product, the competent national authority as well as the Agency should be informed immediately.

The procedure of reporting quality defects or product recalls is outlined on the Agency website.

5. Is it required to keep reference and retention samples of each product?

Annex 19 of the good manufacturing practice guideline for medicinal products gives guidance on the taking and holding of reference samples of starting materials, packaging materials or finished products and the retention samples of finished products.

A reference sample is a sample of a batch of starting material, packaging material or finished product which is stored for the purpose of being analysed should the need arise during the shelf life of the batch concerned.

A retention sample is a sample of a fully packaged unit from a batch of the finished product. It is stored for identification purposes (i.e. for identifying presentations, packaging, labelling, package leaflets, batch numbers or expiry dates) should the need arise during the shelf life of the batch concerned.

Where the product has been re-packaged (e.g. to replace the carton or package leaflet) one full retention sample per repackaging activity of each batch of finished product should be taken, as there is a risk of product mix-up during the assembly process. It is important to be able to identify quickly who is responsible in the event of a mix-up (i.e. original manufacturer or re-packager), as it would affect the extent of any resulting recall.

Reference and retention samples from each batch of finished product should be retained for at least one year after their expiry date. Records of traceability should be maintained and be available and accessible for review by the competent authorities at any time.

6. What is a product with special conditions for distribution imposed on the marketing-authorisation holder?

A medicinal product with special conditions for distribution is a product which can only be distributed under specific conditions, such as the requirements for educational materials, patient alert cards or controlled distribution system.

If any specific conditions are mentioned in the annex of the marketing authorisation for the product, it is the responsibility of the Member States to implement these conditions and restrictions. However, the parallel distributors are also required to liaise with the marketing-authorisation holder and the national competent authorities in the Member State of destination to discuss the requirements they may need to meet before distributing the medicinal products and to include the information required as per the annex (e.g. patient alert card) and/or relevant national legislation.

The marketing-authorisation holder and the national competent authorities are mainly responsible for agreeing the details of controlled distribution systems and the details of the operation of surveillance programmes. In case a parallel distributed product has not been first put on the market of the Member State of destination by the marketing-authorisation holder, the parallel distributor and the national competent authorities should ensure that there is a controlled distribution system, a surveillance programme as well as an educational programme in place (e.g. physician’s pack, patient alert card, etc.), if appropriate, which achieves the aims of the systems required by the conditions of the marketing authorisation for parallel distributed medicinal products.

Notification of changes/ bulk changes/ annual update

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1. What are the two types of a notification of changes?

Mandatory changes due to the urgent safety updates: notifications of changes resulting from urgent safety updates to the product information shall be submitted within a three month timeframe of the notification by the Agency of the urgent safety update having occurred. Notifications of changes submitted due to an urgent safety update will not be subject to any fee when submitted within three months, and will not affect the 'birthday date' of the annual update. No other scopes of changes can be added to such notifications.

Optional notification of changes: can be used to submit new information for one particular EU presentation. These notifications will incur the same fee as the annual update, but they will not affect the 'birthday date' of the annual update. The applicable fee is payable per EU presentation.

The changes may be implemented only after the notice of changes has been issued.

2. What is the scope of a bulk change?

The scope(s) of changes that can apply to a bulk change are limited to:

  • a change in the name and/or address of a parallel distributor,
  • addition or deletion of a re-packager,
  • and/or a change in the name and/or address of a re-packager.

The change to the bulk may be implemented only once the notice of a bulk change is issued.

3. What is an annual update?

The annual update is the procedure that allows the Agency to have an overview of the medicinal products distributed in parallel. By the annual update the parallel distributor notifies the Agency of any changes introduced to the medicinal product through the last year. The annual update is mandatory for every medicinal product except for dormant products (see, question 'What happens if the product is not distributed for the last 12 months?' below).

Products distributed for 12 months with no changes (no new annex, no new Member States of origin/destination, no changes of labelling, no new re-packagers etc.) still require a completed annual update form, indicating ‘no changes’ and a signed cover letter, but will not be subject to a fee.

The annual update is a 'DO and TELL' procedure. A parallel distributor can implement changes and only inform the Agency about these changes with the next annual update. The annual update comprises both: mandatory changes due to the urgent safety updates and optional notification of changes. Only mandatory changes due to the urgent safety update notified no later than three months before “birthday date” can be the part of the annual update.

1 application per product, pharmaceutical form & Member State of destination = 1 fee

Example: A company holds PD notices for all four pharmaceutical forms of 'product X':

  • tablets;
  • orodispersible tablets;
  • oral solution;
  • solution for injection.

This parallel distributor has to submit four annual updates for 'product X', one for each pharmaceutical form.

4. What is the relation between the annual update, the notification of changes and the bulk change?

The notification of changes or the annual update procedure can be used to introduce the same changes to the medicinal product.

The annual update however needs to be submitted every year even if all the changes were notified by the notification of changes. Consequently, the annual update allows the Agency to have an overview of the medicinal products distributed in parallel. The Agency recommends that parallel distributors notify all of the changes through the annual update.

The bulk change is a procedure of a different scope than the annual update and the notification of changes.

5. What happens if the product is not distributed for the last 12 months?

If the medicinal product has not been distributed in parallel for the last 12 months it requires the completed annual update through which the product can be indicated as 'dormant', but will not be subject to a fee. During the period of dormancy the annual update does not need to be submitted.

If the medicinal product is marked dormant, the letters of dormancy will be issued. They will be sent to the parallel distributor, the MAH and the national competent authorities. Products notified to be dormant will be removed from the PD register.

If the parallel distributor wishes to re-introduce the medicinal product to the market in parallel, he shall submit the annual update for the said product. Once the annual update notice has been issued, the medicinal product will be reintroduced to the PD register and can be distributed in parallel again.

6. What is the 'birthday date' of an annual update?

The 'birthday date' of an annual update is the date by when an annual update must be submitted. The first 'birthday date' is counted from the date of the last PD notice issued for a certain pharmaceutical form of a particular product for each Member State of destination, prior to 01/05/2013. When no PD notice for a certain pharmaceutical form of a particular product for each Member State of destination had been issued prior to 01/05/2013, the birthday date is calculated from the date of the first PD notice issued after 01/05/2013.

Example: A parallel distributor holds the following PD notice for ‘product X’ tablets issued on: 5 March 2006, 27 July 2008, 22 December 2008 and 19 February 2013. The first 'birthday date' is February 2014 and the company is required to submit an annual update before the end of February 2014.

The following 'birthday date' will remain the same for all subsequent annual updates. If the first annual update was submitted in February 2013, then the second 'birthday date' will be February 2014. The 'birthday date' can also be moved forward if the annual update is submitted before the set date. If the second 'birthday date' is February 2014, but the annual update is submitted in January 2014 then the third 'birthday date' will be January 2015. This principle also applies to annual updates submitted to reactivate dormant products.

7. When to submit an annual update?

An annual update should be submitted once a year before its 'birthday date' only for those products which have been distributed in the last 12 months and/or for those products which will be distributed in the next 12 months.

One application per product & pharmaceutical form & Member State of Destination = 1 fee.

After the submission of the annual update no other documentation is required, except for the notifications of a change due to the urgent safety updates. In the meantime the parallel distributor can begin compiling the new scopes of changes for the next annual update.

It is strongly recommended that the parallel distributors submit only one notification when applying for a notification of an annual update for the first time and wait for the outcome of the parallel distribution notification check in order to avoid the repetition of errors when submitting subsequent notifications.

8. How to submit an annual update?

A notification of an annual update has to be supported with the following documentation:

  • a completed electronic version of the annual update form with all EU presentations grouped according to the scopes of changes;
  • a signed cover letter clearly indicating the name of the medicinal product, the strength, the pharmaceutical form, the pack-size and any other relevant information;
  • colour copies of the outer and inner labelling of only one EU presentation of that particular pharmaceutical form preferably showing the most complicated re-packaging option e.g. re-boxing or re-labelling of a product sourced from a Member States of Origin where non-Latin alphabets are in use; or the colour copies of the new re-packaging method when it is included in the form.
  • additional documents relating to the particular scopes of changes (e.g. prior letter; authorisations, mock-ups etc.);
  • an editable format of the package leaflet (doc, pdf) in the language of the Member State of destination in compliance with the latest version of the EU marketing authorisation;
  • a report extracted from text comparison software (if applicable).

The above documentation should be submitted electronically via Eudralink to: pd_esubmission_changes@ema.europa.eu.

The Subject line of the message should state: 'Date in ICH format (i.e. YYYY.MM.DD)' 'PD Name'_'Product Name'_ 'pharmaceutical form'_'Annual update' (see, section 'Initial notification').

9. Text comparison software report

In cases where the check of the package leaflet has to be completed (i.e. when there is a change in the package leaflet), a text comparison report submitted with an annual update/notification of changes will attract a reduced fee. The report should serve as a proof that the submitted package leaflet is in compliance with the latest annex.

The Agency does not recommend any particular text verification software. It should be text comparison software that preserves data integrity of the documents (i.e. the software should not change the file formats for the text comparison). The created report should ideally juxtapose the deviations in table form. It should be designed to detect the following deviations between the package leaflet and the text of the annex:

Change:Text found in the leaflet which replaces the text in the annex.

Deviation:Text found in the leaflet that is not identical to the one in the annex, e.g. typos, grammatical mistakes etc. Please note, if an error is found in the annex, the parallel distributor should inform the Agency by mentioning the error in the report.

Deletion:Text found in the annex which is not in the leaflet.

Insertion:Text found in the leaflet which is not in the annex.

Hyphenation: Change due to a software-generated hyphen inserted at the end of the line or due to an addition or removal of a hyphen – the Agency software interprets a missing hyphen as a deletion.

Case: Upper and lower case differences.

Space: Change due to space inserted between characters vs. no space.

Style changes

Bold: Changed font style (whether text is bold or not).

Italic: Changed font style (whether text is italic or not).

Underline: Change due to text being underlined or not.

Size: Changed font size – please make sure to follow the readability guidelines (font equivalent to Times New Roman 9 for package leaflet).

Sub/Super: Change between regular, superscripted, or subscripted text.

The submitted report must not contain deviations with the exception of the date of the latest revision as well as the following:

Acceptable deviations in the report

  • The revision date of the most recent published annex;
  • Deletion: Text found in the annex which is not in the leaflet: e.g. more manufacturers in the annex, but fewer in the package leaflet;
  • Insertion: Text found in the leaflet which is not in the annex: e.g. parallel distributor and re- packager’s details, internal code, trademark symbol or sentence;
  • Deviation: Text found in the leaflet that is not identical to the one in the annex: e.g. correction of typos or grammatical mistakes etc.;
  • Size: Changed font size – please make sure to follow the readability guidelines; font size must be equivalent to at least Times New Roman 9 for the package leaflet.

Any other deviations will be considered as mistakes and will result in the payment of the full fee if not justified in the submitted report or in the cover letter.

Fees

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1. What are the administrative fees payable to the Agency in relation to parallel distribution?

Pursuant to Article 8 (3) of Regulation (EC) 297/95 'a fee shall apply for administrative services where the information required in the case of parallel distribution has to be checked.' In case of non-payment the Executive Director may refuse to perform the administrative service and return the notification to the parallel distributor or to suspend the service until the fee has been paid, including the relevant interest, Article 10 (3) of Regulation (EC) 297/95.

2. How does the invoicing system work?

The fee due date is the date when the Agency determines the total fee amount that is due for an application or service. In the case of parallel distribution, the fee due date corresponds to the date of submission of the notification and the parallel distributor’s obligation to pay that fee starts on that date.

The Agency’s terms and conditions for payment of fees stipulate that an invoice is payable 30 days from the invoice date. That represents the deadline for the parallel distributor to settle the payment.

The invoice is sent to the billing address indicated by the parallel distributor and contains clear details of the product(s) involved, the amount of the fee, the bank account to where the fee should be paid and the due date for payment.

An application for parallel distribution can be withdrawn without any charges on the day of the submission.

3. Fees for an initial notification

A full fee for the parallel distribution notification check is applicable to each EU presentation of a medicinal product per Member State of destination.

If the official language in different Member States of destination is the same (e.g. United Kingdom, Ireland and Malta; Germany and Austria; Greece and Cyprus), only one fee is applicable.

The fee covers the parallel distribution notification check and any subsequent safety updates relating to the initial notification triggered and adopted by the Committee for Medicinal Products for Human Useor the Committee for Medicinal Products for Veterinary Use.

4. Fees for an annual update

Each annual update is subject to a fee. This fee covers all EU presentations for one pharmaceutical form of a certain product per Member State of destination or for several Member States of destination having the same official language.

A reduced fee is applicable to each annual update if supported with a report generated through text comparison software which meets the specific conditions listed in the section about ‘Text comparison software report’.The quality of the reports will be monitored by random checks of the package leaflets with the purpose of confirming their validity. The reduced fee only applies, where a parallel distribution notification check of the package leaflet is required (i.e. update of the annex, addition of re-packager to leaflet, etc.).

5. Fees for a notification of changes

Each notification of changes is subject to a fee. This fee shall cover one EU presentation of a medicinal product for one Member State of destination having one or more official languages, or for several Member States of destination having the same official language.

A reduced fee is applicable to each notification of changes if supported with a report generated through text comparison software which meets the specific conditions listed in the question ‘Text comparison software report’.

The quality of the reports will be monitored by random checks of the package leaflets with the purpose of confirming their validity. The reduced fee only applies, where a parallel distribution notification check of the package leaflet is required (i.e. update of the annex, addition of re-packager to leaflet, etc.).

6. Fees for bulk changes

Each notification of bulk changes is subject to a fee. This fee shall cover all of a parallel distributor’s initial notifications approved by the date of submission of the notification of bulk changes. The scope(s) of the changes are limited to: a change in the name and/or address of a parallel distributor, addition or deletion of a re-packager, and/or a change in the name and/or address of a re-packager. For more information, see fee regulations.

7. Further information on the fee structure of the Agency and relevant EU legislation

More information on the fee structure can be found through the links below:

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