Type-IA variations: questions and answers

This page lists questions that marketing-authorisation holders (MAHs) may have on type-IA variations. It provides an overview of the European Medicines Agency's position on issues that are typically addressed in discussions or meetings with MAHs in the post-authorisation phase. Revised topics are marked 'New' or 'Rev.' upon publication.

A PDF version of the entire post-authorisation guidance is available:

Updated 25/03/2025:
Questions marked with "Rev. Mar 2025"

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure

Reference Number: EMEA-H-19984/03 Rev. 112

European Medicines Agency post-authorisation procedural advice for users of the centralised procedure: document with track changes

Reference Number: EMEA-H-19984/03 Rev. 112

These questions and answers have been produced for guidance only and should be read in conjunction with the rules governing medicinal products in the European Union, volume 2, notice to applicants.

MAHs must in all cases comply with the requirements of Community legislation. Provisions that extend to Iceland, Liechtenstein and Norway by virtue of the European Economic Area agreement are outlined in the relevant sections of the text.

1. When shall I submit my Type IA/IAIN variation(s)? Rev. Mar 2025

Commission Regulation (EC) No 1234/2008 , as amended ('the Variations Regulation') and the Commission guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 and on the documentation to be submitted pursuant to those procedures ('the Variations Guidelines') set out a list of changes to be considered as type-IA variations. Such minor variations have only a minimal impact or no impact at all, on the quality, safety or efficacy of the medicinal product, and do not require prior approval before implementation ('do-and-tell' procedure). The Classification Guideline clarifies the conditions that must be met in order for a change to be considered a type-IA variation.

Such minor variations are classified in two subcategories, which impact on their submission:

Type-IA variations requiring immediate notification ('IA_IN')

The Classification Guideline specifies the type-IA variations that must be notified (submitted) immediately to the national competent authorities or European Medicines Agency following implementation, in order to ensure the continuous supervision of the medicinal product.
 

Type-IA variations NOT requiring immediate notification ('IA')

Type IA variations implemented in 2024 and not submitted to the Agency by 31 December 2024:

Type IA variations that do not require immediate notification may be submitted by the marketing authorisation holder (MAH) no later than 12 months after implementation.

The 12 months deadline to notify minor variations of Type IA allows for an ‘annual reporting’ for these variations, where a MAH submits several minor variations of Type IA which have been implemented during the previous twelve months.

Type IA variations implemented from 1 January 2025 (inclusive):

Type IA variations which do not require immediate notification should be collected and submitted by the marketing authorisation holder (MAH) as a ‘Type IA annual update’, within 12 months after the oldest variation IA implementation date. The submission should be done as a single submission covering all minor variations of Type IA implemented during the period. The application should be submitted no earlier than 9 months and no later than 12 months after the first implementation date of the Type IA variation included in the ’Type IA annual update’.

As an example, if an applicant has three Type IA variations to the same marketing authorisation implemented on 1 February 2025, 7 March 2025 and 21 April 2025 respectively, an annual update of Type IA variation grouping the three variations would be expected between 1st November 2025 (9 months after 1st February 2025) and 1st February 2026 (12 months after 1st of February 2025), since the first implementation date of the variations included in the grouping is 1st of February 2025, unless one of the exceptions below applies.

A submission outside the Type IA annual update is possible in the following cases:

• as part of an acceptable grouping together with variations of other types (IAIN, IB or II).
• as part of a super-grouping (one or more Type IA variations for multiple marketing authorisations from the same MAH).
• when a single Type IA variation in an annual update was refused and the company needs to resubmit to comply with the 12 months reporting period.
• exceptionally, an individual submission immediately after implementation when duly justified. This encompasses the following cases listed below:
  • When the Type IA variation is needed to mitigate a shortage, and regulatory flexibilities have been agreed with the MSSG (Executive Steering Group on Shortages and Safety of Medicinal Products).
  • When the Agency deems the immediate update of the marketing authorisation dossier in relation to a public health concern necessary (e.g. an emerging or declared public health emergency).
  • When the Type IA variation is needed to update the marketing authorisation dossier prior to a routine site inspection or a MAH transfer.
  • When a third country is requesting proof of acceptance in EU (e.g. by the means of a Certificate of Pharmaceutical Product (CPP) or EU authorisation letter) for a particular change intended to mitigate a shortage or a critical need in the third country or the medicinal product is part of an international reliance program that has been accepted by the Agency.

The Type IA annual update must fulfil the conditions for grouping or super-grouping, if it concerns more than one Type IA variation and/or more than one marketing authorisation:

• all Type IA variations affect the same marketing authorisation approved via centralised procedure, or
• the Type IA variation(s) affect several marketing authorisations approved via centralised procedure owned by the same holder, provided that the variation(s) notified is/are identical for all marketing authorisations concerned (“super-grouping”).

Please note that currently it is not operationally possible to have super-grouping of Type IA variations including simultaneously marketing authorisations approved via the centralised procedure and non-centralised procedure. Additional cases taking into account the experience acquired may be identified in the future and appropriate operational guidance will be provided on Agency and CMDh websites accordingly.

In line with the objective of a single review and to ensure its effectiveness, it is expected that the individual supporting data for the variation(s) applying to the several marketing authorisations are identical.

It is also not acceptable to combine a grouping with a super-grouping in the same application (i.e. having variations not applicable to all marketing authorisations concerned). Separate submissions should be done in such case.

Most Type IA variations do not impact the product information. However, in case of an upcoming submission of a variation, extension or other regulatory procedure which will affect the product information, the MAH should also include any Type IA change(s) affecting the product information as part of a grouping application, in order to keep the product information up-to-date and to facilitate document management.

Meaning of implementation for type-IA variations

For quality changes, 'implementation' is when the company makes the change in its own quality system. This interpretation allows companies to manufacture conformance batches and generate any needed stability studies to support a type-IA_IN variation before making an immediate notification because the change will not be made in their own quality system until these data are available.

For product information, it is when the company internally approves the revised product information. The revised product information will then be used in the next packaging run.

2. Can I (super-) group the submission of Type IA/IAIN variations? Can they be grouped with other types of variation? Rev. Mar 2025

Groups of Type IA variations:

Article 7(2)(a) of the Variations Regulation, as amended, sets out the possibility for a MAH to group several Type IA/IA_IN variations to the terms of the same marketing authorisation under a single notification to the same relevant authority.

Possible grouping of Type IA/IA_IN changes only

• Several Type IA and/or Type IA_IN affecting one medicinal product:
   

  
• This means for instance that a Type IA variation, which is normally not subject to immediate notification, can be included in the submission of a Type IA_IN variation, if they are related.

Supergroups of Type IA variations:

Article 7(a) of the Variations Regulation sets out the possibility for a MAH to super-group one or several Type IA/IA_IN variations to the terms of more than one marketing authorisations under a single notification to the same relevant authority.

Possible super-grouping of Type IA/IA_IN changes only:

• one Type IA or IA_IN affecting several medicinal products from the same MAH authorised through the centralised procedure, provided that the variation is the same for all medicinal products.

• several Type IA and/or Type IA_IN affecting several medicinal products from the same MAH authorised through the centralised procedure, provided that those variations are the same for all medicinal products.

  

When the grouping includes only Type IA variations that do not require immediate notification, the submission should be done as part of the Type IA annual update, unless otherwise permitted by the Agency (see question When shall I submit my Type IA/IA_IN variation(s)?).

Possible grouping of Type IA/IA_IN with other types of variations:

• Type IA/IA_IN can also be grouped with other variations (e.g. Type IB, Type II, Extension), as listed in Annex III of Commission Regulation 1234/2008, as amended. Groupings not included in the aforesaid Annex should be discussed and agreed with the Agency prior to submission.
• Such grouped submissions will follow the review procedure of the highest variation in the group. Please also refer to “What type of variations can be grouped?”.

It must be noted however, that when submitting Type IA/ IA_IN variations as part of a group, the legal deadlines for submission of each variation should be respected i.e. a Type IA_IN should always be submitted immediately, whether or not it is grouped with other variations, and Type IA variations should be submitted as part of an annual update, unless a submission outside the Type IA annual update is accepted.

3. Is the (co-)rapporteur involved in the review of type IA / IAIN variations? Rev. Mar 2025

The Agency will review the notification within 30 days following receipt, without involvement of the Rapporteur or Co-Rapporteur.

The same principle applies whether a single or a (super-)group of Type IA/ IA_IN variations is being submitted.

However, if the Type IA/ IA_IN variations are grouped with other variations (Type IB, Type II, Extension), the grouped submission will follow the review procedure and timelines of the highest variation in the group and the Rapporteur will provide an assessment report for the group. Although the Rapporteur is not expected to assess the Type IA/IA_IN variations in the group the Rapporteur will confirm in the assessment report whether non-acceptance of (part of) the change(s) in the group leads to non-acceptance of the Type IA/ IA_IN changes in the group.

4. How shall I present and submit my Type IA/IAIN Variation(s)? Rev. Mar 2025

A Type IA/ IA_IN variation notification should contain the elements listed in Annex IV of the Variations Regulation and should be presented in accordance with the appropriate headings and numbering of the EU-CTD format. The Commission ‘Variations Guidelines’ further specifies which elements should be included in a Type IA/ IA_IN variation notification.

In order to help MAHs ensuring that their Type IA/IA_IN variations are complete and correct before submitting them to the Agency, it is strongly recommended to use the 

Pre-notification check for type IA/IAIN variations

Also, in order to facilitate the completion of the application form, MAHs are advised to consult the EMA/CMDh Explanatory Notes on Variation Application Form and the 

European Medicines Agency practical guidance on the application form for centralised type IA and IB variations

Type IA variations are intended to provide for a simple, rapid and efficient procedure for minor changes. The MAH should be aware that the submission of redundant information or a confusing dossier presentation will not facilitate such procedures. Similarly, deficient and missing documentation can lead to rejection of the variation. However, in exceptional cases the Agency may issue a single request for supplementary information, for which a response should be provided within 4 working days in the mandatory eCTD format for electronic submissions. Failure to provide the requested information, or submission of incomplete and/or unsatisfactory responses within 4 working days may lead to an unfavourable outcome.

The following elements should be included in a Type IA/ IA_IN variation notification, as specified in the Variations Guidelines:

eSubmission delivery file

• In order to facilitate the registration of the submission, marketing authorisation holders are required to fill in all the submission attributes through the eSubmission delivery file UI
• Cover letter (for groupings, include a short overview of the nature of the changes).
• Where a variation leads to or is the consequence of other regulatory procedure, a description of the relation between these procedures should be provided in the cover letter and a copy of the request should be annexed.
• For Type IA annual updates, the cover letter and eAF should clearly identify the submission as Type IA annual update.

Procedure number

• The procedure number or case number will be assigned by the EMA only upon receipt of an eCTD application. 

EU variation application form

• The completed electronic EU variation application form (eAF) should include the details of the marketing authorisation(s) concerned, as well as a description of all variations submitted together with their date of implementation. Information on the electronic Application Form for variations can be found in the eSubmissions eAF webpage.
• MAH should pay particular attention when preparing the eAF for (super-)grouping and ensure that all variations included are listed with its corresponding classification code according to the Annex to the Variation Guideline, or Article 5 of the Variation Regulation, and a description of the proposed precise scope is provided for each one.
• Applicable conditions and documentation should be clearly ticked. Explanations on the conditions and required documentation can be added as applicable or a reference on where the information can be found.
• A detailed present and proposed section should also be included for all proposed changes, including editorial changes if applicable.
• Any change not clearly covered by any scope of a variation included (except editorial), and that is not clearly described in the precise scope section of the application form and included in the present and proposed section should not be considered as accepted.
• For a super-grouping affecting several medicinal products, MAHs are reminded to confirm in the application form under “Declaration of the applicant” that the MAs concerned belong to the same MAH and that the main signatory confirms authorisation to sign on behalf of the designated contacts.

Supporting documentation

• Relevant documentation in support of the proposed variation, including all documentation as specified in the Annex should be included in the application.
• If applicable, the revised summary of product characteristics (SmPC or Annex I), annex II, labelling (Annex IIIA) and/or package leaflet (Annex IIIB) should be provided as a full set of annexes. If the change applied for affects Annex A, this should be provided as a separate set of one document per EU language. (See also question on ‘When do I have to submit revised product information? In all languages?’) Additional information on how to comply with this in a required technical format can be found in the Harmonised eCTD Guidance.
• Please be reminded that in accordance with Union data protection requirements, no personal data should be included in the annotated PIs. This applies to the English version as well as to all the other languages translation versions. The annotated product information files must include the statement containing the procedure number(s) and may be published on the EMA website as part of the product EPAR page. Please submit annotated PIs in an anonymised format (i.e. names of the reviewers removed from the track-changes). If you do not wish to do so, please ensure that the individuals whose data is included consented to its sharing with EMA, the publication on the EMA website and its further sharing by EMA with third parties such as other marketing authorisation applicants, marketing authorisation holders and National Competent Authorities, as relevant. EMA expressly disclaims any liability or accountability for the presence of unnecessary personal data in the annotated PI submitted by the marketing authorisation holder.
• Where the overall design and readability of the outer and immediate packaging and/or package leaflet is affected, the need for the provision of mock-ups or specimens should be discussed with the Agency Labelling Office on a case-by-case basis.
• For super-grouping, the supportive documentation for all variations concerned should be submitted as one integrated package with a common cover letter and common application form referring to all medicinal products and variations concerned as stated above. The present-proposed section of the application form should clearly identify the relevant CTD sections in support of each variation and indicate the precise present and proposed wording for each change, including editorial changes if applicable.
• In addition, for each medicinal product the relevant supportive documentation and revised product information (if applicable) should be provided in one sequence per medicinal product, in order to allow the Agency to update the dossier of each marketing authorisation with the relevant updated/new information. Cross-references to any documentation submitted for another medicinal product can therefore not be accepted. For further details, please refer to “How shall I present a grouped variations application?” and to the Harmonised technical eCTD Guidance.

It should be noted that the responsibility for the quality of the submitted documentation lies with the MAH and is crucial to the overall process. The MAH is responsible for ensuring that the Type IA variation complies fully with the conditions and documentation requirements as specified in the Variations guidelines. 

Submission of Type IA/ IA_IN Variation Notifications

Information is available on ‘Submitting a post-authorisation application’.

References

• Regulation (EC) No 726/2004
• Commission Regulation (EC) No 1234/2008
• Commission Regulation (EU) No 712/2012 amending Regulation (EC) No 1234/2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products
• Guidelines on the details of the various categories of variations, on the operation of the procedures laid down in Chapters II, IIa, III and IV of Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products and on the documentation to be submitted pursuant to those procedures
• Electronic Variation application form
• Variation application form, The Rules governing Medicinal Products in the European Union, Notice to Applicants, Volume 2B
• EMA/CMDh Explanatory Notes on Variation Application Form (CMDh/EMA/133/2010)
• European Medicines Agency practical guidance on the application form for centralised type IA and IB variations
• Pre-notification check for type IA/IAIN variations
• Article 5 Recommendation

5. How shall my Type IA/ IAIN variation be handled (timetable)? Rev. Mar 2025

The Agency will review the ((super-)grouped) Type IA/ IA_IN variation(s) within 30 calendar days following receipt. The Agency will check the correctness of the application form, the presence of the required documentation and compliance with the required conditions, in accordance with the Classification guideline.

Receipt of Type IA/ IA_IN variation notification                             Day 0

Start of Agency check                                                               Day 1

Favourable/Unfavourable review outcome                                 by Day 30

By day 30, the Agency will inform the MAH about the outcome of the review.

Where the outcome of the procedure is favourable and the Commission Decision granting the Marketing Authorisation requires amendments, the Agency will inform the Commission accordingly.

Where one or several Type IA/ IA_IN variations are submitted as part of one notification, the outcome will clearly indicate which scopes(s)/changes(s) have been accepted or rejected following its review.

Type IA/ IA_IN changes should be implemented prior to submission of the notification. However, in case of unfavourable outcome, the Variations Regulation requires the MAH to immediately cease applying the rejected variation(s). Please refer to “What should I do in case of an unfavourable review outcome for my Type IA/ IA_IN variation?” for further details.

It is still possible for MAHs to submit Type IA notifications prior to its implementation, when the proposed changes are related to other notifications/variations requiring prior approval. The expected implementation date should be clearly stated in the application form.

 

6. Can my Type IA/ IAIN be part of worksharing? Rev. Mar 2025

In accordance with the provisions of Article 20 of the Variations Regulation, the worksharing procedure does not apply to Type IA/ IA_IN variations.

However, the submission of one or several Type IA/ IA_IN variations affecting more than one marketing authorisation of the same MAH, in one notification to the same relevant authority (similar to worksharing) is possible under Article 7a of the Regulation – see also “Can I (super)group the submission of Type IA/ IA_IN variations? Can they be grouped with other types of variations?”

In addition, it is also possible to group a Type IA/ IA_IN variation(s) with a Type IB or Type II variation, which is submitted for a worksharing procedure. In such case, the Rapporteur will be asked to confirm whether the non-acceptance of (part of) the change(s) leads to non-acceptance of the Type IA/IA_IN variation(s). In this case, the 'high level' cross-products procedure number for the worksharing should be requested to the Agency. 

For further information see also Worksharing: questions and answers ‘What procedure number will be given to variation applications under worksharing”

7. What should I do in case of an unfavourable outcome for my Type IA/ IAIN variation(s)? Rev. Mar 2025

A Type IA/ IA_IN variation will be fully or partially rejected when:

• The classification of the proposed change(s) in incorrect
• not all of the conditions for the Type IA/ IA_IN variation are met
• the submitted documentation as required by the Variations Guidelines is deficient or inaccurate, including provision of the product information Annexes and Annex A, if affected by the change(s) applied for.

In such case, the MAH shall immediately cease to apply the rejected changes.

In case of a negative outcome of a Type IA application because the conditions for the Type IA variation(s) are not met and consequently a resubmission (as a Type IB, Type II variation or Extension or additional Type IA variations) is needed or because documentation is deficient, the MAH should revert the impacted sections of the regulatory dossier back to the latest approved version by means of a consolidating eCTD sequence within 15 days. The MAH is also responsible to judge whether the rejected Type IA variation has an impact on the quality, safety or efficacy of the medicinal product. If this is the case, the MAH has to take appropriate action.

The Agency may ask the MAH to complete a suspected quality defect notification form and provide a Risk Assessment report on the impact of the product on the market via e-mail to [e-mail] within 7 calendar days from the date of the rejection letter. Such requests are expected to be very exceptional. The MAH has to follow the instructions under Quality defects and recalls.

8. What fee do I have to pay for a Type IA/ IAIN variation? Rev. Dec 2024

There is no fee payable for type IA/IAin variations.

References

• Fees payable to the European Medicines Agency

 

9. Do I have to submit mock-ups and specimens?

For information concerning submission of mock-ups and specimens in the framework of post-authorisation procedures, please refer to Checking process of mock-ups and specimens of outer / immediate labelling and package leaflets of human medicinal products in the centralised procedure, 3.4 other post-authorisation procedures.

Reference

• Checking process of mock-ups and specimens of outer / immediate labelling and package leaflets of human medicinal products in the centralised procedure

10. What changes will trigger new EU number(s) (additional presentation(s))? Rev. Mar 2025

Any changes in the number of units of medicinal product or medical device being an integral part of the medicinal product (e.g. prefilled syringes) will trigger a different EU number.

Differentiation should be made between the addition of a presentation where the two presentations will co-exist on the market on a long-term basis versus a replacement of a presentation where the new presentation will replace the previous one (it is expected that for a certain period of time, the two presentations will co-exist on the market until the stock of the previous presentation runs out).

In principle, a replacement of one presentation by another presentation does not trigger a new EU number, unless the number of units of medicinal product or medical device being an integral part of the medicinal product (e.g. prefilled syringes) is changed.

Examples of changes in presentations for replacement, not triggering a new EU number (this is not an exhaustive list):

• Replacement of the primary or secondary packaging,
• Changes in the number of medical devices not being integral part of the medicinal product,
• Change in composition (e.g. change in excipients),
• Change in units per blisters (without change to the total number of units per pack).

Examples of changes in presentations for replacement, triggering a new EU number (this is not an exhaustive list):

• 30 to 60 tablets,
• 2 prefilled syringes containing the medicinal product instead of one prefilled syringe.

In case of addition, as the presentations will co-exist on the market, two packs with different contents cannot be covered by the same EU number and will be considered as different presentations.

Changes in the number of any unit (not restricted to the medicinal product) or changes in the specifications of any unit (not restricted to the medicinal product) contained in the pack will trigger a new EU number.

Examples of changes that will trigger new EU numbers (this is not an exhaustive list):

• Introduction of an alternative injection kit with a different number of syringes or swabs,
• Introduction of an alternative syringe of different volume or an alternative syringe with a needle guard,
• Introduction of an alternative immediate (primary) packaging made from a different material,
• Introduction of an alternative shape/dimension of a pharmaceutical form (pre-rolled sealant matrix versus flat, change in size of patch). 

11. How to obtain new EU sub-numbers for Type IAIN variation concerning an additional presentation (e.g. new pack-size)? Rev. Mar 2025

In the specific case of a Type IA_IN variation for an additional presentation, the new EU marketing authorisation sub-number should be requested from the Agency before implementation.

The request should be sent together with a 

Checklist for requesting new EU sub-numbers (type IAIN and Type IB lead procedures only)

and a draft Annex A (in English only) through the EMA Service Desk, selecting the tab “Business Services”, category “Human Regulatorhe subcategory to be selected is “Post-authorisation - Human”, followed by the sub-option: “New EU number request”.  The request should be may”. Tde at least 5 working days in advance of the intended submission of the variation. Once a number has been allocated, this number should subsequently be included in the Annex A and product information annexes submitted together with the Variation notification.

12. When do I have to submit revised product information? In all languages? Rev. Feb 2025

In case the Type IA/ IA_IN notification affects any of the annexes, i.e. annex A, SmPC, annex II, labelling and/or package leaflet, the affected revised product information Annexes must be submitted as follows:

• All EU language versions - Complete set of Annexes electronically only in Word format (highlighted) and in PDF (clean)

The 'complete set of Annexes' includes Annex A (if applicable), I, II, IIIA and IIIB i.e. all authorised presentations (if applicable), SmPC, labelling and PL texts for all strengths and pharmaceutical forms of the product concerned, as well as Annex II. The complete set of Annexes must be presented sequentially (i.e. Annex I, II, IIIA, IIIB) as one document for each official EU language. Page numbering should start with "1" (bottom, centre) on the title page of Annex I. If annex A is affected, the document should also be provided in all EU official languages as a separate set. 

The 'QRD Convention' published on the Agency website should be followed. When submitting the full set of Annexes in PDF format, this should be accompanied by the completed 

Checklist for the submission of Type IA and Type IB (without linguistic review) product information annexes and Annex A (if applicable) - human

A user guide on how to generate PDF versions of the product information and annexes is also available.

Please be reminded that in accordance with Union data protection requirements, no personal data should be included in the annotated PIs. This applies to the English version and as well as all the other languages translation versions. The annotated product information files must include the statement containing the procedure number(s) and may be published on the EMA website as part of the product EPAR page. Please submit annotated PIs in an anonymised format (i.e. names of the reviewers removed from the track-changes). If you do not wish to do so, please ensure that the individuals whose data is included consented to its sharing with EMA, the publication on the EMA website and its further sharing by EMA with third parties such as other marketing authorisation applicants, marketing authorisation holders and National Competent Authorities, as relevant. EMA expressly disclaims any liability or accountability for the presence of unnecessary personal data in the annotated PI submitted by the marketing authorisation holder. 

The electronic copy of all languages should be provided as part of the variation application. Highlighted changes should be indicated via 'Tools – Track Changes'. Clean versions should have all changes 'accepted'.

Icelandic and Norwegian language versions must always be included.

The Annexes provided should only reflect the changes introduced by the Variation(s) concerned. However, in exceptional cases where MAHs take the opportunity to introduce minor linguistic or typographical corrections in the texts this should be clearly mentioned in the cover letter and in the scope section of the application form.

In addition, the section “present/proposed” in the application form should clearly list the minor linguistic or typographical corrections introduced for each language. Alternatively, such listing may be provided as a separate document attached to the application form. Any changes not listed, will not be considered as part of the variation application.

In such cases and in cases where any other ongoing procedure(s) may affect the product information Annexes, the MAH is advised to contact the Agency in advance of submission or finalisation of the procedure(s) concerned.

When the Type IA/ IA_IN Notification concerns several medicinal products, the relevant complete set of product information Annexes should be included in the eCTD sequence for each product concerned.

For Type IA/ IA_INvariations affecting Annex A (e.g. introduction of a new presentation), translations of the revised Annex A in all EU languages should be provided as separate documents in clean PDF format and EN tracked Word, together with the variation application. Where the variation introduces (a) new EU sub-number(s), this/these should be included in the Annex A and in the product information texts as part of the variation application (see also “How to obtain new EU sub-numbers for a Type IA_IN variation concerning an additional presentation (e.g. new pack-size)”?).

Similarly, in case of a deletion of a pharmaceutical form/strength/pack-size(s), the amended Annex A and product information Annexes should be provided as part of the Variation application.

13. How and when will the updated product information Annexes become part of the Marketing Authorisation? Rev. Mar 2025

For Type IA/ IA_IN variations affecting the product information Annexes to the Commission Decision, the Commission Decision will be updated within one year.

By the end of this period, the Agency will send the complete set of Annexes, based on the latest (previously) approved Annexes and reflecting the Type IA/ IA_IN change(s) agreed during the past year together with a line-listing of those Type IA/ IA_IN notification(s). The Commission will subsequently issue a Commission Decision on the Type IA/ IA_IN notification(s) concerned.

However, where an Opinion affecting the Annexes which is followed by an immediate Commission Decision, e.g. listed in the Article 23.1a(a), is transmitted to the Commission within this yearly period the changes of the Type IA/ IA_IN notification(s) concerned will already be included in the Annexes to that Opinion and will consequently be reflected in the resulting Commission Decision. This Commission Decision will therefore replace the yearly updating of the MA for the Type IA/ IA_IN notification(s) concerned.

At the occasion of a next Type IA/ IA_IN variation affecting the Annexes, the procedure outlined above will be repeated based on the new ‘Reference point’ of the next Type IA/ IA_IN concerned.

(See also diagram below, which illustrates the updating process.)

In addition, it is important that in case of an upcoming submission of a variation, extension or other regulatory procedure which will affect the product information, the MAH should also include as a grouping application any Type IA change(s) affecting the product information that have not been previously notified, in order to keep the product information up-to-date and to facilitate document management.

Where a Type IA/ IA_IN notification concerns several marketing authorisations, the Commission will update the marketing authorisation with one Decision per marketing authorisation concerned.

14. What should be the date of revision of the text for Type IA Variations? Rev Mar 2025

Type IA/IA_IN variations do not require prior approval before implementation (“Do and Tell” procedure), i.e. they can be implemented and notified to the Agency either immediately for Type IA variations requiring immediate notification (‘IA_IN’) or within 12 months for Type IA variations not requiring immediate notification (‘IA’) as an annual update, or outside the annual update if one of the exceptions applies.

For Type IA variations affecting the product information, the date of revision of the text to be included in section 10 of the summary of product characteristics and in the corresponding section of the package leaflet at the time of printing should be the date of implementation of the change by the Marketing Authorisation Holder.

The meaning of “implementation” is explained in ”When shall I submit my Type IA/IA_IN variation(s)”?

15. Who should I contact if I have a question when preparing my application or during the procedure? Rev. July 2023

If you cannot find the answer to your question in the Q&A when preparing your application, please contact us via EMA Service Desk, selecting the tab “Business Services”, category “Human Regulatory”. The subcategory to be selected is “Post-authorisation - Human”, followed by the sub-option “Variation IA queries”.

The Agency aims to respond to your query within 10 working days. To help us deal with your enquiry, please provide as much information as possible including the name of the product in your correspondence.

You should submit your query once and it is important that you submit it using the applicable type of question and sub-option. If you are uncertain on a classification of a variation as type IA or type IB please use only one of the sub-options “Variation IA queries” or “Variation IB A&B scopes queries” or “Variation IB C scopes queries”. Your query will be channelled internally to the relevant service(s) that will respond to you.

If you do not have an EMA Account, you may create one via the EMA Account Management portal. For further information or guidance about how to create an EMA Account reference the guidance "Create an EMA Account".

Type IA variations will be handled by a dedicated team of Procedure Managers (PM). You will be able to contact this PM throughout the procedure.