Type-IB variations: questions and answers

This guidance only applies to procedures initiated under Regulation (EC) No 1234/2008 and Regulation (EU) No 712/2012. before 28 January 2022.

Once a veterinary product has received approval from the Commission (the “Commission Decision”) all further procedures connected with the product will fall under “Post-Authorisation Procedures”.

The guidance published under Post-authorisation procedural Q&A provides an overview for different types of post-authorisation procedures that occur frequently and, in each case, addresses a number of questions which marketing authorisation holders (MAHs) may have.

Applicants should use the eSubmission Gateway / Web Client for all veterinary procedural submissions to the Agency. For more information, including links to guidance on registration with the system, see the Veterinary eSubmission website.

Additional information

The Rules governing Medicinal Products in the European Union, Volume 6, Notice to Applicants
Community Legislation
Commission Regulation (EC) No 1234/2008 - referred to as the ‘Variations Regulation’
Commission Regulation (EU) No 712/2012 amending Regulation (EC) No 1234/2008
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 (2013/C 223/01) - referred to as the ‘Variations Guidelines’, and also as the ‘Classification Guideline’ or the ‘Procedural Guideline’

The Variations Regulation defines a minor variation of Type IB as a variation which is neither a Type IA variation nor a Type II variation nor an Extension. Such minor variations must be notified to the National Competent Authority/European Medicines Agency ('the Agency') by the Marketing Authorisation Holder (MAH) before implementation, but do not require a formal approval. However, the MAH must wait a period of 30 days to ensure that the application is deemed acceptable by the National Competent Authority/the Agency before implementing the change (“Tell, Wait and Do” procedure).

The Variations Guidelines outlines changes which are considered as Type IB variations. In addition, any change which is not an Extension and whose classification is not determined taking into account the Variations Guidelines and the recommendations delivered pursuant to Article 5 of the Variations Regulation, is considered a Type IB variation by default. For such changes which are submitted as Type IB variations by default (so-called ‘z’ classifications), the Agency will determine during validation whether the proposed classification as a Type IB variation is appropriate before the start of the evaluation procedure. See also 'How shall my Type IB variation be handled (timetable)?'.

When one or more of the conditions established in the Variations Guidelines for a Type IA variation are not met, the concerned change may be submitted as a Type IB variation unless the change is specifically classified as a major variation of Type II.

References

: Upon validation of the notification by the Agency, the rapporteur will be involved in the evaluation of Type IB variations. (See 'How shall my Type IB variation be handled (timetable)'?)
The co-rapporteur is not involved in the assessment of Type IB variations.

MAHs may choose to group the submission of several Type IB variations for the same product into one application. It is also possible for a MAH to group a Type IB variation with other variation(s) for the same product (e.g. Type IA, Type II, Extension), where applicable.

Allowed groupings are listed in Annex III of the Variations Regulation. Other groupings have to be agreed in advance with the Agency. Any proposal to group clinical and quality variations should be adequately justified.

Such grouped submissions will follow the review procedure of the highest variation in the group. Please also refer to theQ&A: Grouping of variations.

Where the same minor Type IB variation(s) affect more than one marketing authorisations from the same MAH, the MAH may choose to submit these variations as one application for 'worksharing'. Please also refer to Q&A: Worksharing of variations.

References

A Type IB variation application 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 dossier format.

The Variations Guidelines further specifies which elements should be included in a Type IB variation application:

Cover letter (for groupings, include a short overview of the nature of the changes and indicate whether it is an allowed grouping in Annex III of the Variations Regulation or the grouping has been agreed with the Agency).
If a variation is submitted because it has been requested as an outcome arising from another pre-/post-authorisation procedure (including as a result of a PSUR or post-authorisation measure (PAM) e.g. condition, specific obligation, recommendation), then this should be clearly mentioned in the cover letter for the resulting variation, identifying the related EMA procedure number from which the variation arose. In case the reference number for the PAM has not been confirmed by the Agency, a description of the commitment/measure is sufficient at time of submission (or contact vet.applications@ema.europa.eu to check for the PAM reference number).
The completed EU variation application form (as published on the eAF eSubmission website), including the details of the marketing authorisation concerned. Where a variation is considered a Type IB by default (‘z’ scope within the most relevant classification), a detailed justification for its submission as a Type IB application must be included. MAHs are reminded that the variation application form should be signed by the official contact person. Should the official contact person not be available, an official letter of authorisation confirming the delegation of signature to a different person should be enclosed. In order to facilitate the completion of the application form, MAHs are advised to consult the Agency's practical guidance on the application form for centralised type IA and IB variations. practical guidance on the application form for centralised type IA and IB variations
Reference to the respective extract of the Variations Guidelines, or reference to the published Article 5 Recommendation, sed for the relevant application, if applicable. Applicable conditions and documentation should be clearly ticked on the extract provided, or marked as not applicable if that is the case. If a condition or documentation is not applicable, this should be explained and a justification for its absence should be provided. The extract(s) can be submitted as a separate annex in module 1.2.
Relevant documentation in support of the proposed variation including all documentation as specified in the Variations Guidelines.
For variations submitted to implement changes requested by the Agency, where no new additional data are submitted by the MAH, a copy of the request should be annexed to the cover letter.
For procedures affecting the product information without need for linguistic review, the revised summary of product characteristics (SPC or Annex I), annex II, labelling (Annex IIIA) and/or package leaflet (Annex IIIB) as a full set of annexes per EU language (Word highlighted and PDF clean) should be provided.
If the change affects Annex A, it should be provided as a separate document per EU language (Word highlighted and PDF clean). (See specific requirements for procedures with and without linguistic review in sections 'When do I need a linguistic review for changes in the product information?' and 'How should I submit revised product information? In all languages?')
Where the overall design and readability of the outer and immediate packaging and/or package leaflet is affected, the Agency might request the Applicant to provide specimens and mock-ups on a case-by-case basis. (See also “Do I have to submit mock-ups?”)

Grouped variations

For grouped variations concerning one marketing authorisation, all variations must be declared in the variation application form. The documentation requirements for each type of variation in the group must be adhered to. However, the supportive documentation for all variations concerned should be submitted as one integrated package (i.e. there is no need to submit a separate documentation package for each variation).The present-proposed section of the application form should clearly identify the relevant dossier sections in support of each variation. For grouped variations concerning more than one marketing authorisation please refer to 'What is worksharing and what types of variations can be subject to worksharing?'.

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 variation complies fully with the data and documentation requirements as specified in the Variations Guidelines. The MAH should pay particular attention to grouped variations, for which each change and the related supportive documentation should be clearly identified.

Submission of Type IB variation applications

The variation application presented in the correct format should be submitted to the Agency.

Where applicable, revised product information Annexes should be provided in electronic (Word and PDF) format (see also 'When do I have to submit revised product information? In all languages?').

All submissions for centrally authorised products (CAP) sent to EMA via the eSubmission Gateway/Web Client will be considered delivered to all National Competent Authorities (NCA)’ representatives, alternates and scientific experts.

References

There are no recommended submission dates for Type IB variations with no changes to the product information or Type IB variations with changes to the product information which do not require linguistic review, however, MAHs are encouraged to avoid submitting Type IB variation applications shortly before or during the Agency holiday periods (e.g. end of July and Christmas).

The Agency has published Recommended submission dates for centralised and maximum-residue-limit procedures

A linguistic review will be performed for Type IB variations affecting the product information where the wording has not been provided by the Agency in all languages prior to the start of the procedure.

Some examples of Type IB variations where a linguistic review will not be performed are:

C.I.2.a) Change in the Summary of Product Characteristics, Labelling or Package Leaflet of a generic/hybrid/biosimilar medicinal product following assessment of the same change for the reference product;
Deletion of information from the product information.

A separate set of recommended submission dates is applicable for Type IB variations included in a worksharing submission or for Type IB variations submitted as part of a group including Type II variations and/or extensions (included in the same document, Recommended submission dates for centralised and maximum-residue-limit procedures

Where the CVMP requests a Type IB variation following the assessment of a PSUR, post-authorisation measure (condition/specific obligation/recommendation), following adoption of class-labelling or requests a Type IB variation for generic/hybrid/biosimilar medicinal products following assessment of the same change for the reference product, MAHs must submit the corresponding variation application at the latest within 2 months following the adoption of the relevant assessment conclusion.

Variation applications reflecting the outcome of an Urgent Safety Restriction (USR) shall be submitted to the Agency immediately and in any case no later than 15 days after the initiation of the USR. This applies to USRs initiated by the MAH or imposed by the European Commission.

References

Upon receipt of a Type IB application, the Agency will handle the application as follows:

a) Handling of Type IB variations included in the Variations Guidelines (‘foreseen’) or covered by an Article 5 recommendation:

The Agency will check within 5 working days whether the variation is correct and complete ('validation') before the start of the evaluation procedure.

DAY	ACTION
Day x	Receipt of Type IB variation
Day x+1	Start of Agency validation
Day x+5	Agency validation (in case of missing information, this period will be extended)

Issues identified during validation will be notified to the MAH by email. The MAH will be requested to provide responses to the issues raised within 5 working days. Delayed or insufficient responses will lead to complete or partial invalidation (in case of groupings) of the application as only one request for supplementary information will be issued during the validation phase.

The Agency will send to the MAH a confirmation of the positive outcome of the validation and the start date of the procedure.

DAY	ACTION
Day 1	Start of evaluation
by Day 20	Receipt of rapporteur's assessment report
by Day 30	(Non-)acceptance of the variation

Within 30 days following the acknowledgement of receipt of a valid application, the Agency will notify the MAH of the outcome of the procedure, and the Commission, if the Commission decision granting the marketing authorisation requires any amendments. If the Agency has not sent the MAH its opinion on the application within 30 days, the application shall be deemed acceptable.

In case of an unfavourable outcome the MAH may, within 30 days, amend the application to take due account of the grounds for the non-acceptance of the variation. If the MAH does not amend the application as requested, the application shall be rejected.

Within 30 days of receipt of the amended application, the Agency will inform the MAH of its final (non‑)acceptance of the variation, and the Commission, if the Commission decision granting the marketing authorisation requires any amendments.

Where Type IB variations affect the Annexes to the marketing authorisation, such changes can be implemented without awaiting the 12-monthly update of the Commission decision and the agreed change(s) should be included in the Annexes of any subsequent regulatory procedure.

b) Handling of Type IB variations claimed by the MAH to be unforeseen IB variations by default (so-called ‘z’ classifications):

The Agency will check within 5 working days whether the proposed change can be considered a minor variation of Type IB, and whether the application is correct and complete ('validation') before the start of the evaluation procedure. In exceptional cases, the Agency may have to consult with the rapporteur on the appropriate classification of the variation, which may lead to a slightly longer validation period (up to 10 working days).

When the Agency is of the opinion that the proposed variation may have a significant impact on the quality, safety or efficacy of the medicinal product, the MAH will be notified that the applied change cannot be handled as Type IB and that the variation will have to be reclassified as a Type II variation. As a consequence, the

MAH will be requested to revise and supplement their variation application so that the requirements for a Type II variation application are met.

Following receipt of the valid revised variation application, a Type II assessment procedure will be initiated according to the Agency procedural timetables for Type II variations.

When the Agency is of the opinion that the proposed variation can be considered a Type IB variation, the MAH will be informed of the outcome of the validation and of the start date of the procedure. The Type IB application will be handled as set-out in section a) above.

c) Handling of groupings of minor variations (Type IB/Type IA)

For grouping of minor variations, where not all of the changes applied for can be positively validated, all valid and not valid variations will be clearly listed in the validation outcome document.

Where a Type IB by default variation, within a group of variations, has to be reclassified as a Type II variation, the MAH will be requested to confirm whether this variation should remain in the group. If confirmed, the whole group will be handled as a Type II variation, as set out in section b) above.

Where several Type IB variations are submitted as part of one application, it will be clearly specified in the final Agency notification which variation(s) have been accepted or rejected following assessment, unless some of the variations have been withdrawn by the MAH during the procedure (see 'How will grouped variation applications be handled (timetable)? What will be the outcome of the evaluation of a grouped application?').

References:

For information on the fee applicable for Type IB variations, please refer to the Fees payable to the European Medicines Agency. The fee covers all authorised strengths, pharmaceutical forms and presentations of a given medicinal product.

For variations introducing additional presentations or pack-sizes, each additional presentation or pack-size attracts separate fees (x additional presentations = x separate fees). Each presentation or pack-size should therefore be declared as a separate variation on the variation application form under the section ‘variations included in this application’.

Grouped Type IB variations, whether consequential or not, will each attract a separate Type IB fee.

The Agency will issue an invoice following the notification of the administrative validation to the applicant and fees will be payable within 30 calendar days of the date of the invoice. The invoice will be sent to the billing address indicated by the MAH and will contain clear details of the product and procedures involved, the type of fee, the amount of the fee, the bank account to where the fee should be paid and the due date for payment.

Applicants requiring a purchase order number or similar references on the invoice are requested to clearly indicate it on the cover letter or application form accompanying the dossier, as well as in the “Customer reference” box of the delivery file to be generated for submission via the EMA Gateway. The Agency does not accept standalone notifications of purchase order numbers that are not associated with a dossier.

For Type IB variations, if the variation is considered ‘invalid’ (i.e. an assessment process cannot be started), an administrative fee will be charged by the Agency.

References

: Please consult the.

Where the Type IB application affects SPC, labelling and/or package leaflet, the affected revised product information Annexes must be submitted as follows:

If a linguistic review will not be performed, the complete set of Annexes in all EEA languages should be provided as part of the variation application, in Word format (highlighted tracked changes) and in PDF (clean).
If a linguistic review will be performed, only the English version of the complete set of Annexes should be provided as part of the variation application, in Word format (highlighted tracked changes). The Agency will send the MAH the timetable for the linguistic review process at validation. The complete set of revised language versions will need to be provided 5 calendar days after validation of the application according to the instructions provided within the aforementioned timetable.
The ‘complete set of Annexes’ includes Annex I, II, IIIA and IIIB i.e. all SPC, labelling and package leaflet 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. All Annexes should be in compliance with the QRD Convention published on the Agency website. When submitting the full set of Annexes in PDF format, the formatting checklist and the user guide on how to prepare PDF versions of the product information should be followed.
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 amendments in the texts or to align the product information with the latest QRD template, this should be clearly mentioned in the cover letter and in the ‘precise scope and background’ section of the application form. In addition, the section “present/proposed” in the application form should clearly list the minor linguistic amendments introduced for each language. Alternatively, such listing may be provided as a separate annex 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.
For those variations which affect the 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 Word and PDF formats, together with the variation application. Where the variation introduces a new EU sub-number, the sub-number should be requested from the Agency before submission and should subsequently be included in the SPC, labelling and PL texts as part of the variation application (see also “How to obtain new EU sub-numbers before submitting a Type IB variation for an additional presentation?”). In case of a deletion of a pharmaceutical form/strength(s), such prior liaison with Agency is not required, and the amended Annex A and product information Annexes should be provided as part of the variation application.

References

Any changes in the number of units of veterinary medicinal product 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 veterinary medicinal product 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,
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 veterinary 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 veterinary 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 syringe of different volume,
Introduction of an alternative immediate (primary) packaging made from a different material,
Introduction of an alternative shape/dimension of a pharmaceutical form.

If you have any questions on any upcoming submission, please contact vet.applications@ema.europa.eu.

: In the specific case of a Type IB variation for an additional presentation, the new EU marketing authorisation sub-number should be requested from the Agency before submission.
The request should be sent together with a draft Annex A (in English only) to vet.applications@ema.europa.eu with a copy to the product-shared mailbox and should be made 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 application.

For Type IB variations affecting the annexes to the Commission Decision, the Commission Decision will generally be updated within one year, unless the Type IB variation concerns any of the changes listed in Article 23.1a(a), for which the Commission Decision will be updated within two months. This would include variations related to the addition of a new therapeutic indication or modification of an existing one, addition of a new contraindication or change in posology. It is expected that such variations would be processed as Type IB variations mainly in the framework of generics and hybrids following changes to the product information of the reference medicinal product.

However, all Type IB variations affecting the annexes can be implemented without awaiting the update of the marketing authorisation and the agreed Type IB changes should be included in the annexes of any subsequent regulatory procedure.

For Type IB variations subject to yearly update of the respective Commission Decision, at the end of this yearly period, the Agency will send the complete set of annexes, based on the latest approved annexes and reflecting the Type IB changes introduced during the past year as well as a line-listing of those variations pending update of the Commission Decision.

Where a notification contained several Type IB variations concerning one marketing authorisation, the Commission will update the marketing authorisation with one single decision to cover all the approved minor variations.

However, where a notification or opinion affecting the annexes that is followed by an immediate Commission Decision is transmitted to the Commission within this yearly period, the changes of the Type IB notifications concerned will already be included in the annexes to the notification or opinion and will consequently be reflected in the resulting Commission Decision. This Commission Decision will therefore replace the yearly updating of the marketing authorisation for the Type IB notifications concerned.

On the occasion of the next Type IB variation affecting the annexes, the procedure outlined above will be repeated based on the new reference point of the next Type IB concerned (see also diagram below, which illustrates the 12-monthly updating process).

References

General principles

The European Commission Variations Guidelines specify that “If amendments to the dossier only concern editorial changes, such changes should generally not be submitted as a separate variation, but they can be included in a variation concerning that part of the dossier. In such cases the changes should be clearly identified in the application form as editorial changes and a declaration that the content of the concerned part of the dossier has not been changed by the editorial changes beyond the scope of the variation submitted should be provided”. Changes that can be classified as a variation according to the Variations Guidelines are not considered editorial changes and should be submitted under the appropriate variation category.

The Agency strongly recommends the submission of editorial changes within procedures that have an administrative validation phase (e.g. type IB or type II variations. This allows the appropriate review of proposed editorial changes during validation and the consequential amendment of the submission prior to assessment, if needed. The editorial changes proposed should affect the same part of the dossier concerned by the variation procedure. For example, if a variation affects Part 2.C, editorial changes can be submitted in Part 2.C.

Exceptionally, the Agency may accept minor editorial changes as part of IA variations, if affecting the same dossier sub-section impacted by the variation submitted. This is due to the fact that IA notifications are administrative in nature and do not have a validation phase. The Agency expects MAHs to keep proportionality between the submissions of editorial changes versus the real change of the variation. In case of doubt about the acceptability of editorial changes in future type IA applications, MAHs are advised to contact vet.applications@ema.europa.eu in advance of the submission.

MAHs are reminded to follow this guidance and to ensure the high quality of variation applications in support of a timely processing of these submissions.

Editorial changes should generally not be submitted as a separate variation and therefore no reference to a variation category is required when they are encompassed within another variation procedure.

Within the ‘Precise scope and background…’ section of the variation application form, the MAH should provide:

a brief description of the proposed editorial changes and a justification as to why they are considered ‘editorial’ (i.e. why they should not trigger a specific variation);
a declaration confirming that the changes proposed as editorial do not change the content of the concerned part(s) of the dossier beyond the scope of the variation within which the editorial changes are being submitted;
confirmation that all relevant parts of the dossier have been updated accordingly and are included within the variation package.

Additionally, all the editorial changes should be listed in the present/proposed table (or provided as a separate annex that is cross-referred to from this table), identifying each related change in the dossier down the lowest section heading and page numbers where possible.

Any changes proposed by the applicants as editorial will be carefully considered by the Agency at time of submission and may be subject to further assessment at the same time as the overarching variation. Proposed editorial changes that cannot be accepted as such will be rejected. In case of doubt, applicants can contact vet.applications@ema.europa.eu in advance of the planned submission.

Editorial changes in Part 2 (quality)

The following may be considered as examples of editorial changes to Part 2: adding headers for ease of use, reordering of existing information without changing the meaning, alignment of information among/within the sections provided the correct reference that had been previously agreed can be demonstrated (e.g. alignment of information in flow charts to process description), punctuation changes and grammar/orthographic corrections that do not alter the meaning of the text.

Examples of changes that cannot be considered editorial: removal of specification parameters or manufacturing description, update of information to bring the dossier content in line with the current manufacturing process, etc.

Proposed changes that require confirmation by the rapporteur may only be accepted when submitted within the scope of an upcoming variation type IB or type II which impacts upon the corresponding section of Part 2.

If editorial changes are required and there is no upcoming procedure, the MAH may consider submitting these changes as a separate, default Type IB variation (B.I.z or B.II.z, as appropriate).

Editorial changes in Parts 3 (safety & residues) and 4 (pre-clinical & clinical)

Editorial changes in Parts 3 and 4 are not foreseen. Please contact vet.applications@ema.europa.eu in advance of an upcoming submission.

Editorial changes to the product information in Part 1.B (SPC, labelling and package leaflet)

Formatting changes, correction of typographical errors and/or mistakes to the English product information or other linguistic versions of the product information are considered editorial changes provided that the meaning of the text is not altered. These changes can be included within the scope of any upcoming procedure impacting on the product information.

Changes in the scientific content or meaning cannot be accepted as an editorial change. These changes should be classified under the scope of the relevant category in accordance with the Variations Guidelines (e.g. Type II, C.I.4).

Proposed changes that may require confirmation by the rapporteur or linguistic review will only be accepted when submitted within the scope of an upcoming variation Type IB or Type II under chapter C (of the Variations Guidelines) which impacts upon the product information and where linguistic review is foreseen, if applicable.

Should there be no upcoming regulatory procedure in which to include the editorial changes, these could also be submitted as a stand-alone, default Type IB variation e.g. under C.I.z if they affect the English product information. If other languages are affected and in case no procedure affecting the product information is upcoming, MAHs are advised to contact vet.applications@ema.europa.eu to discuss how to handle these necessary changes.

The MAH should liaise with the Agency without delay if the mistake concerns an incorrect or missing important information (e.g. contra-indication or adverse event), in the English or any of the other language versions, that could affect the safe and effective use of the medicinal product and/or lead to potential medication errors (e.g. wrong strength, wrong posology, wrong route of administration).

References

The introduction of a new pack size (i.e. additional to currently approved pack sizes) should be submitted as a variation under sub-indent B.II.e.5.a) according to the Variations Guidelines.

Range is defined from the smallest to the biggest approved pack size (not from '0') for the same pharmaceutical form and strength. The pack size equals the number of units of the pharmaceutical form (e.g. tablets, sachets, ampoules, etc.) contained per outer packaging. Pack sizes not included within this range are considered to be outside of the range.

For the addition of a new pack size where the number of units of the pack is within the range of the currently approved pack sizes for the strength and pharmaceutical form, applicants should submit a variation B.II.e.5.a.1 (IA_IN).

For the addition of a new pack size where the number of units of the pack is outside the range of the currently approved pack sizes for the strength and pharmaceutical form, applicants should submit a variation B.II.e.5.a.2 (IB).

In support of a timely introduction of new pack sizes to the market, the EMA accepts the following approach for the introduction of various pack sizes falling outside the range within a single grouped submission. The biggest or the smallest pack size per strength outside the range should be classified as B.II.e.5.a.2 (IB). This presentation defines the new limits of the range so that any intermediate pack size for the strength and pharmaceutical form can be classified as B.II.e.5.a.1 (IA_IN).

Some examples are provided below to illustrate the principles explained above.

Example 1

Example 2

Example 3

The 20 mg strength of 'Veterinary Medicinal Product A' currently has two approved pack sizes of 30 and 60 tablets for the pharmaceutical form 'film-coated tablets' and the MAH intends to apply for two new pack sizes of 90 and 120 tablets at the same time. The introduction of a new pack size of 120 tablets for the 20 mg strength is considered outsidethe range of packs and should be classified as variation B.II.e.5.a.2 (IB). This pack size defines a new limit for the range (30-120), so that the introduction of a pack size of 90 tablets can be classified as a variation B.II.e.5.a.1 (IA_IN). The MAH should therefore apply for a grouped variationof 1 x type IB - B.II.e.5.a.2 and 1 x type IA_IN - B.II.e.5.a.1.

Example 4

The 20 mg and 40 mg strengths of 'Veterinary Medicinal Product B' currently each have two approved pack sizes of 2 and 10 pre-filled syringes for the pharmaceutical form 'solution for injection'. The MAH intends to apply for four new pack sizes:

5 and 30 pre-filled syringes for the 20 mg strength;
5 and 30 pre-filled syringes for the 40 mg strength

For the 20 mg strength, the introduction of a new pack size of 5 pre-filled syringes strength is considered within the range of approved packs (2-10)and should be classified as variation B.II.e.5.a.1 (IA_IN) and the introduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10) and should be classified as variation B.II.e.5.a.2 (IB).

For the 40 mg strength, the introduction of a new pack size of 5 pre-filled syringes strength is considered within the range of approved packs (2-10)and should be classified as variation B.II.e.5.a.1 (IA_IN) and the introduction of a new pack size of 30 pre-filled syringes is considered outsidethe range of approved packs (2-10)and should be classified as variation B.II.e.5.a.2 (IB).

The MAH should therefore apply to the EMA for a grouped variation for the abovementioned scopes.

Example 5

The 50 mg strength of 'Veterinary Medicinal Product C' currently has two approved pack sizes of 10 and 30 tablets for the pharmaceutical form'film coated tablets' and the MAH intends to apply for a multipackof 30 (3x10) tablets. The introduction of a multipack 30 (3x10) tablets for the 50 mg strength is considered within the range of approved packs (10-30) and should be classified as variation B.II.e.5.a.1 (IA_IN).

IMPORTANT

For variations introducing additional presentations or pack sizes, each additional presentation or pack size attracts separate fees (x additional presentations = x separate fees). Each presentation and pack size should therefore be declared as a separate variation on the variation application form under the section 'variations included in this application'.
Changes to strength, pharmaceutical form and route of administration are to be submitted as an extension of a marketing authorisation.

References

Topics

Guidance

Type-IB variations: questions and answers

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