General Note: In case of a change in therapeutic indication, posology or maximum daily dose, a review of quality documentation should be performed. Any resulting change to the quality documentation (for example, the need to change impurity limits) will require the submission of the appropriate quality variation under the Quality Changes chapter.
C.5 Change in the legal status of a medicinal product for centrally authorised medicinal products
C.6 Change(s) to therapeutic indication(s)
C.8 Introduction of a summary of pharmacovigilance system for medicinal products
#c1
| C.1 Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a Union referral procedure | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) The medicinal product is covered by the defined scope of the procedure | 1 | 1, 2, 3 | IAIN |
| (b) The medicinal product is not covered by the defined scope of the procedure but the change(s) implements the outcome of the procedure and no new additional data is required to be submitted by the holder | 1, 2, 3 | IB | |
| (c) The medicinal product is not covered by the defined scope of the procedure but the change(s) implements the outcome of the procedure with new additional data submitted by the holder | II | ||
| Conditions | |||
| 1. The variation implements the wording exactly as requested by the authority and it does not require the submission of additional information and/or further assessment. | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: a reference to the Commission Decision concerned or to the agreement reached by the CMDh (as applicable) with the annexed summary of product characteristics, labelling or package leaflet. | |||
| 2. Confirmation that the proposed summary of product characteristics, labelling and package leaflet is identical for the concerned sections to that annexed to the Commission Decision or to the agreement reached by the CMDh (as applicable). | |||
| 3. Revised product information. | |||
#c2
| C.2 Change(s) in the summary of product characteristics, labelling or package leaflet of a generic/hybrid/biosimilar medicinal products following assessment of the same change for the reference product | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Implementation of change(s) for which no new additional data is required to be submitted by the holder | 1, 2, 3 | IB | |
| (b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the marketing authorisation holder (e.g. comparability) | II | ||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: EMA/NCA request, if applicable. | |||
| 2. Revised product information. | |||
| 3. For the biosimilar medicinal product aligning the product information with an indication of the reference medicinal product: a justification that the comparability exercise performed for the biosimilar medicinal product is valid for the applied indication. | |||
#c3
| C.3 Change(s) in the summary of product characteristics, labelling or package leaflet intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Article 45 or 46 of Regulation (EC) No 1901/2006, or the outcome of a PRAC signal recommendation, or to adapt to a joint recommendation of EU competent authorities (e.g. a Core SmPC, or following the assessment of an Urgent Safety Restriction etc.) | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Implementation of the agreed wording | 1 | 1, 2 | IAIN |
| (b) Implementation of the agreed wording that requires additional minor assessment (e.g. translations are not yet agreed upon) | 1, 2 | IB | |
| (c) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH | II | ||
| Conditions | |||
| 1. The variation implements the wording exactly as requested, including agreed national translations, and it does not require the submission of additional information and/or further assessment. | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authorities. | |||
| 2. Revised product information. | |||
#c4
| C.4 Change(s) in the summary of product characteristics, labelling or package leaflet due to new quality, preclinical, clinical or pharmacovigilance data. | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| II |
#c5
| C.5 Change in the legal status of a medicinal product for centrally authorised medicinal products | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) For generic/hybrid/biosimilar medicinal products following an approved legal status change of the reference medicinal product | 1, 2 | IB | |
| (b) All other legal status changes | II | ||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: proof of authorisation of the legal status change (e.g. reference to the Commission Decision concerned). | |||
| 2. Revised product information. | |||
| Note: for nationally authorised medicinal products approved via MRP/DCP, the change of the legal status is to be handled at national level (not via a MRP variation). | |||
#c6
| C.6 Change(s) to therapeutic indication(s) | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Addition of a new therapeutic indication or modification of an approved one | II | ||
| (b) Deletion of a therapeutic indication | 1 | IB | |
| Documentation | |||
| 1. Amendment of the relevant section(s) of the dossier, including revised product information. | |||
| Note: where the change takes place in the context of the implementation of the outcome of a referral procedure, or – for a generic/hybrid/biosimilar product – when the same change has been done for the reference product, variations C.1 and C.2 apply, respectively. | |||
#c7
| C.7 Deletion of: | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) a pharmaceutical form | 1, 2 | IB | |
| (b) a strength | 1, 2 | IB | |
| Documentation | |||
| 1. Declaration that the remaining product presentation(s) are adequate for the dosing instructions and treatment duration as mentioned in the summary of product characteristics. | |||
| 2. Revised product information. | |||
| Note: in cases where a given pharmaceutical form or strength has received a marketing authorisation which is separate to the marketing authorisation for other pharmaceutical forms or strengths, the deletion of the former will not be a variation but the withdrawal of the marketing authorisation. | |||
#c8
| C.8 Introduction of a summary of pharmacovigilance system for medicinal products | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Introduction of a summary of pharmacovigilance system after a change of the holder | 1, 2 | IAIN | |
| Documentation | |||
| 1. Summary of the pharmacovigilance system:. Proof that the holder has at its disposal a qualified person responsible for pharmacovigilance and a statement signed by the holder to the effect that it has the necessary means to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC. | |||
| 2. PSMF number (if available). | |||
| Note: This variation is only applicable to nationally authorised medicinal products. | |||
#c9
| C.9 Introduction of, or change(s) to, the obligations and conditions of a marketing authorisation, including the risk management plan | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| (a) Implementation of changes to reflect the outcome of previous assessment | 1 | 1, 2 | IAIN |
| (b) Implementation of changes which require additional minor assessment (e.g. change to the due date of obligations and conditions of a marketing authorisation and required pharmacovigilance activities in the risk management plan, including changes to the due date of study milestones, and template updates) | 2 | IB | |
| (c) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the holder where significant assessment by the competent authority is required | II | ||
| Conditions | |||
| 1. The variation implements the action requested, including the exact agreed wording and the agreed national translations, and it does not require the submission of additional information and/or further assessment. | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: A reference to the relevant decision of the competent authorities. | |||
| 2. Update of the relevant section of the dossier. | |||
| Note: This variation covers the situation where the only change introduced concerns the conditions and/or obligations of the marketing authorisation, including the risk management plan and the conditions and/or obligations of marketing authorisations under exceptional circumstances and conditional marketing authorisation. | |||
#c10
| C.10 Inclusion or deletion of black symbol and explanatory statements for medicinal products in the list of medicinal products that are subject to additional monitoring | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| 1 | 1, 2 | IAIN | |
| Conditions | |||
| 1. The medicinal product is included or removed from the list of medicinal products that are subject to additional monitoring (as applicable). | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: A reference to the list of medicinal products that are subject to additional monitoring. | |||
| 2. Revised product information. | |||
| Note: This variation covers the situation where the inclusion or deletion of the black symbol and explanatory statements is not done as part of another regulatory procedure (e.g. renewal or variation procedure affecting the product information). | |||
#c11
| C.11 Submission of results of assessments carried out on target patient groups in order to comply with Article 59(3) of Directive 2001/83/EC and any resulting change(s) to the package leaflet. | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| 1, 2 | IB | ||
| Documentation | |||
| 1. Results of consultation with target patient groups (user test or bridging report). | |||
| 2. Revised product information. | |||
#c12
| C.12 Other variations not specifically covered elsewhere in this Annex which involve the submission of studies, including bioequivalence studies, to the competent authority | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| II | |||
| Note: This variation scope includes the submission of studies where no changes to the summary of product characteristics, labelling or package leaflet are initially proposed by the MAH. . In cases where the assessment by the competent authority of the data submitted leads to a change of the summary of product characteristics, labelling or package leaflet, the relevant amendment to the summary of product characteristics, labelling or package leaflet is covered by the variation. | |||
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