This is an archived version. Please see the current version here: C. SAFETY, EFFICACY, PHARMACOVIGILANCE CHANGES
C.I.5 Change in the legal status of a medicinal product for centrally authorised products
C.I.6 Change(s) to therapeutic indication(s)
#ci1
| C.I.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 MAH | 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 MAH | 1, 3 | II | |
| Conditions | |||
| 1. The variation implements the wording requested by the authority and it does not require the submission of additional informaiton 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. A declaration 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. | |||
#ci2
| C.I.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 MAH | 1, 2 | IB | |
| b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH (e.g. comparability) | II | ||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: EMA/NCA request, if applicable. | |||
| 2. Revised product information. | |||
#ci3
| C.I.3 Change(s) in the Summary of Product Characteristics, Labelling or Package Leaflet of human medicinal products intended to implement the outcome of a procedure concerning PSUR or PASS, or the outcome of the assessment done by the competent authority under Articles 45 or 46 of Regulation 1901/2006 | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Implementation of wording agreed by the competent authority | 1 | 1, 2 | IAIN |
| b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH | 2 | II | |
| Conditions | |||
| 1. The variation implements the wording requested by the competent authority and it does not require the submission of additonal information and/or further assessment. | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: reference to the agreement/assessment of the competent authority. | |||
| 2. Revised product information. | |||
#ci4
| C.I.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 | |||
| Note: This variation does not apply when the new data has been submitted under variation C.I.13. In such cases, the change(s) in the SmPC, labelling and/or package leaflet is covered by the scope of variation C.I.13. | |||
#ci5
| C.I.5 Change in the legal status of a medicinal product for centrally authorised 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 Products approved via MRP/DCP, the change of the legal status is to be handled at national level (not via a MRP variation). | |||
#ci6
| C.I.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 | IB | ||
| 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.I.1 and C.I.2 apply, respectively. | |||
#ci7
| C.I.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 authorization which is separate to the marketing authorization for other pharmaceutical forms or strengths, the deletion of the former will not be a variation but the withdrawal of the marketing authorization. | |||
#ci8
| C.I.8 Introduction of, or changes to, a summary of pharmacovigilance system for medicinal products for human use* | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Introduction of a summary of pharmacovigilance system, changes in QPPV (including contact details) and/or changes in the Pharmacovigilance System Master File (PSMF) location | 1, 2 | IAIN | |
| Documentation | |||
| 1. Summary of the pharmacovigilance system, or update of the relevant elements (as applicable): – Proof that the applicant has at his disposal a qualified person responsible for pharmacovigilance and a statement signed by the applicant to the effect that the applicant has the necessary means to fulfil the tasks and responsibilities listed in Title IX of Directive 2001/83/EC. – Contact details of the QPPV, Member States in which the QPPV resides and carries out his/her tasks – PSMF location | |||
| 2. PSMF (if available) | |||
| Note: This variation covers the introduction of a PSMF irrespective of whether or not the technical dossier of the MA contained a DDPS. Once the Article 57 database is functional, changes in QPPV, including contact details (telephone and fax numbers, postal address and email address) and changes to the location of the PSMF (street, city, postcode, country) may be updated through the Article 57 database only (without the need for a variation). Where the MAH makes use of the possibility to update the above information through the Article 57 database, the MAH must indicate in the marketing authorisation that the updated information of those particulars is included in the database. * For introduction of a new pharmacovigilance system for veterinary medicinal products, please refer to C.II.7. | |||
#ci9
| C.I.9 Change(s) to an existing pharmacovigilance system as described in the detailed description of the pharmacovigilance system (DDPS). | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| a) Change in the QPPV and/or QPPV contact details and/or back-up procedure | 1 | 1 | IAIN |
| b) Change(s) in the safety database and/or major contractual arrangements for the fulfilment of pharmacovigilance obligations, and/or change of the site undergoing pharmacovigilance activities | 1, 2, 3 | 1 | IAIN |
| c) Other change(s) to the DDPS that does not impact on the operation of the pharmacovigilance system (e.g. change of the major storage/archiving location, administrative changes) | 1 | 1 | IA |
| d) Change(s) to a DDPS following the assessment of the same DDPS in relation to another medicinal product of the same MAH | 4 | 1, 2 | IAIN |
| Conditions | |||
| 1. The pharmacovigilance system itself remains unchanged. | |||
| 2. The database system has been validated (when applicable). | |||
| 3. Transfer of data from other database systems has been validated (when applicable). | |||
| 4. The same changes to the DDPS are introduced for all medicinal products of the same MAH (same final DDPS version) | |||
| Documentation | |||
| 1. Latest version of the DDPS and, where applicable, latest version of the product specific addendum. These should include for changes to the QPPV a) summary CV of the new QPPV, b) proof of QPPV EudraVigilance registration, and c) a new statement of the MAH and the QPPV regarding their availability and the means for notification of adverse reactions signed by the new QPPV and the MAH, and reflecting any other consequential changes, e.g. to the organisation chart. When the QPPV and /or QPPV contact details are not included in a DDPS or no DDPS exists, the submission of a revised DDPS version is not required and the application form is to be provided. | |||
| 2. Reference of the application/procedure and product in which the change(s) were accepted. | |||
| Note: C.I.9 covers changes to an existing pharmacovigilance system 1) for veterinary medicinal products and 2) for human medicinal products that have not yet introduced a PSMF. Note for a): Once the Article 57 database is functional, changes in QPPV, including contact details (telephone and fax numbers, postal address and email address) may be updated through the Article 57 database only (without the need for a variation). Where the MAH makes use of the possibility to update this information through the Article 57 database, the MAH must indicate in the marketing authorisation that the updated information of those particulars is included in the database. Note for d): The assessment of a DDPS submitted as part of a new MAA/Extension/Variation may give rise to changes at the request of the national competent authority/EMA in this DDPS. Where this occurs, the same change(s) can be introduced to the DDPS in other marketing authorisations of the same MAH by submitting a (grouped) Type IAIN variation. | |||
#ci10
| C.I.10 Change in the frequency and/or date of submission of periodic safety update reports (PSUR) for human medicinal products | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| 1 | 1, 2 | IAIN | |
| Conditions | |||
| 1. The change in the frequency and/or date of submission of the PSUR has been agreed by the CHMP/CMDh/NCA | |||
| Documentation | |||
| 1. Attached to the cover letter of the variation application: A reference to the agreement of the competent authority (in the case of marketing authorisations granted under the centralised procedure, the CHMP). | |||
| 2. Revised frequency and/or date of submission of the PSUR. (For medicinal products authorised via the centralised procedure, the full set of annexes, including the revised Annex II should be provided) | |||
| Note: This variation applies only when the PSUR cycle is specified in the marketing authorisation by other means than a reference to the list of Union reference dates and where PSUR submission is required. | |||
#ci11
| C.I.11 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 wording agreed by the competent authority | 1 | 1, 2 | IAIN |
| b) Implementation of change(s) which require to be further substantiated by new additional data to be submitted by the MAH where significant assessment by the competent authority is required* | II | ||
| Conditions | |||
| 1. The variation implements the action 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 relevant decision of the competent authority. | |||
| 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. *The introduction of a risk management plan requested by the competent authority always requires significant assessment. | |||
#ci12
| C.I.12 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). | |||
#ci13
| C.I.13 Other variations not specifically covered elsewhere in this Annex which involve the submission of studies to the competent authority* | Conditions to be fulfilled | Documentation to be supplied | Procedure type |
| II | |||
| Note: 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. The inclusion of the Compliance Statement provided for under Article 28(3) of Regulation 1901/2006 is likewise covered by this variation (provided that the requirements under Regulation 1901/2006 have been met). * This variation does not apply to variations that can be considered as Type IB by default under any other section of this Annex. | |||