CMD(v)/BPG/006. BEST PRACTICE GUIDE For. Type II Variations. Edition 00. Edition date:

Transcription

1 Co-ordination Group for Mutual Recognition and Decentralised Procedures - Veterinary EMEA/CMD(v)/115377/2006 BEST PRACTICE GUIDE For Type II Variations Edition 00 Edition date: Implementation date:

2 Page 2 of 10 INDEX 1. Introduction 2. Aim and Scope 3. Reference documents and/or related documents 4.General 5. Type II variation Procedure: 5.1 Pre-submission phase 5.2 Submission phase 5.3 Automatic Validation 5.4 Start of variation procedure 5.5 Evaluation procedure 5.6 Outcome of procedure 5.7 Referral Annex I Time-tables for normal and extended procedure

3 Page 3 of INTRODUCTION This Best Practice Guide is the consequence of the implementation of Commission Regulation (EC) No 1084/2003 from 1 October 2003 and the experience gained through practice with previous BPG, in order to facilitate the notification procedure for Type II variations in a Mutual Recognition Procedure (MRP). Moreover, it is considered that the quality of the submission and supporting documentation, which are the responsibility of the MAH, are crucial to the overall process. 2. AIM AND SCOPE Guidance is given on the role of the Reference Member State (RMS) as co-ordinator of the notification procedure and to reflect good practice of Concerned Member States (CMS) and MAH in handling of Type II variations. This will ensure that the notifications are processed in an efficient and timely manner. Fees will be dealt with on a national basis and are not part of the BPG. 3. REFERENCES AND RELATED DOCUMENTS - Regulation 1084/2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products granted by a competent authority of a Member State. - NTA- Volume 6A- Chapter 5. - CMD(v) BPG for Automatic validation of applications in the Mutual Recognition Procedures. 4. GENERAL For Type II variations, the Marketing Authorisation Holder (MAH) is required to inform the Competent Authorities of the changes to be introduced. Each change applied for has to be accompanied by and specified in the Variation Application Form which is available from the Commission website and additionally national application form if necessary. If a notification requires consequential revision of the Summary of Product Characteristics, label and package insert, it is the responsibility of the MAH to submit these documents, where necessary. The application forms are invalid if these documents are not included in the notification documentation submitted. A consequential variation is defined as an unavoidable and direct result of another change and not simply a change which occurs at the same time (according to the NTA Volume 6A Chapter 5) and may be submitted in a single application according to Article 5 No 3 of Regulation (EC) No 1084/2003. In case of consequential variations, the MAH must include a clear justification/explanation in the variation application form. Changes that cannot be considered as consequential must be submitted as separate (parallel) variation notifications. Reference shall be made to the others in the application form.

4 Page 4 of 10 The proposed timetables for such parallel variations will take into account the longest timetable and the RMS will do his best to finalize them simultaneously. The 60 and 90 day time frames are maximum timelines thus allowing flexibility for shorter procedures in particular situations. The agreed timetable is followed on CTS (Communication Tracking System). 5. TYPE II VARIATION PROCEDURE 5.1 Pre-submission phase MAH is encouraged to undertake prior discussions with the RMS to establish a suitable timeline. It is up to the RMS to propose an accelerated time table to the CMS, to be accepted within the time limit given by the RMS. Nevertheless CMS may object to a shortened procedure based on reasonable grounds, in which case the RMS should propose an acceptable timetable. The MAH may review the documentation with the RMS if considered necessary by both parties. In any case the MAH will contact the RMS at least 7 days prior to the intended submission date to agree a start date and provisional timetable and to obtain the type II procedure number for the variation. The MAH will insert this Type II variation procedure number on page 1 of the application form. RMS creates the procedure in CTS (Communication Tracking System) record for the notification and informs about the new procedure, to the CMSs by sending an via MRVE mailbox. 5.2 Submission phase The MAH will submit simultaneously to the RMS and CMS the following: Application form. Index of the submitted documentation and the corresponding supporting documentation. The MAH should send a fax or identifying the procedure (name of the product and type II variation number) to the RMS. This must include the list of dispatch dates (the dates on which the notification has been sent to the RMS and CMS), The RMS will send an with the relevant information to the CMS. In the case of more than one change to be made at the same time the MAH must submit the appropriate application for each change, at the same time and clearly describe the relation between all these variations. RMS should send an to CMS and MAH with the proposed timetable including validation period. If there is a revised timetable it will also be circulated by the RMS. 5.3 Automatic validation

5 Page 5 of 10 The check of the validity of the application will proceed as described in CMD(v) BPG for Automatic validation of applications in the Mutual Recognition Procedures. 5.4 Start of variation procedure (Day 0) If the RMS receives no notification of an invalid application within 10 working days the RMS acknowledges the receipt of a valid application and starts the evaluation procedure. The RMS informs the MAH and all CMS about the start of the procedure on day 0 by sending an (via the MRVE mailbox for CMS) and updating CTS The Evaluation Procedure Within 40 days ( normal time scale ) or 70 days ( extended time scale ), from the start of the procedure, the RMS shall assess the variation application and prepare a Preliminary Variation Assessment Report (PVAR) including a draft decision and send it to all CMS (via MRVE mailbox) and MAH. The MAH should understand that at this stage of the procedure, the PVAR is for information and transparency purposes only. In the draft decision, the RMS must clearly indicate whether it endorses the variation in its proposed form or if it considers that the variation must be rejected or amended. If considered appropriate, supplementary information can be required from the MAH. Grossly deficient applications will be recommended for refusal without a request for supplementary information. If the RMS considers that any SPC changes proposed by the MAH are not acceptable, the RMS should produce an alternative proposal. After discussion with the applicant the wording of the SPC can be harmonised according to SPCs of other similar products approved recently in the MRP, or according to an approved MR-SPC or to a Commission Decision following an Article 33 (of Directive 2004/28/EC amending the Directive 2001/82/EC) procedure. SPC changes should be focused on the points directly related to the variation application, or consequential upon it. The revision of other sections of the SPC is not acceptable, unless previously agreed as a matter of policy by the CMDV to comply with updated Guidelines or for other reasons of harmonisation. The RMS will highlight such changes in the assessment report. CMSs must clearly express their position (approval or not, via MRVE mailbox) on day 55 (normally 15 days following receipt of the PVAR and draft decision presented by the RMS, according to the flow-charts below). If a CMS sends no comments, the RMS will consider that the CMS accepts the proposal of the RMS. The CMS are responsible for updating the CTS whenever comments are sent. If a CMS does not accept the proposed variation or the draft decision of the RMS, the CMS must give the grounds for its position in the above mentioned comments and clearly indicate, what kind of supplementary information (if any) is required from the MAH.

6 Page 6 of 10 Additionally, the CMS may propose, as SPC Points for consideration, changes to the SPC. The number of these proposals should be kept to a minimum, and the proposals should directly relate to the points subject to the variation. If the RMS or any of the CMS does not endorse the variation proposed by the MAH, the RMS will compile a list of all questions and SPC comments received from the CMS and send this compiled document to the MAH as a request for supplementary information (RSI) (Day 60). A copy will be circulated to the CMS via MRVE mailbox. The RMS should give a clear deadline to the MAH for submitting the responses on the questions (maximum 60 days )The RMS will stop the clock during this period.. The RMS may liase with the MAH as necessary during the clock-off period in case clarification of the questions or responses is required. The RMS must inform the CMS of the deadline given to the MAH. If the MAH cannot respond within due time frame, the variation should be withdrawn. The MAH may resubmit the complete documentation in a new application when new data are available. After receiving the supplementary information and revised SPC where necessary from the MAH, the RMS assesses the new data and prepares the Final Variation Assessment Report (FVAR) including a revised Draft Decision. The clock is restarted when the FVAR, and a revised SPC if applicable are circulated to all CMS via MRVE mailbox for comments. A copy is sent to the MAH for information. The FVAR and amended SPC should be circulated by the RMS within 60 days of receipt of the response. 5.6 Outcome of Procedure Following receipt of the FVAR and revised SPC, if applicable, all CMS shall accept the draft decision and inform the MAH and the RMS via MRVE mailbox (Day 85). In the case of any disagreement between the RMS and CMS which may lead the variation procedure to arbitration, the RMS and the MAH should be informed immediately by the CMS via . If any CMS is unable to agree with the decision of the RMS within the time period mentioned (Day85), the matter shall be referred to arbitration according to Article 39 (2) of Directive 2001/82/EC as amended by those CMS which are against the opinion of the RMS. In case of a refusal of the variation application by both the RMS and the CMS, the MAH may refer the matter to arbitration within 10 days of the end of the procedure. The MAH may withdraw the variation application from all CMS and the RMS at any stage. The application can be withdrawn from a single CMS only if this CMS is removed completely from the list of CMSs for the involved product, i.e. the licence is withdrawn in this country. Withdrawing the product from one or more CMS by the applicant based on disagreements during the variation procedure will not avoid a referral. When the variation is approved, the RMS will notify CMS and MAH of the completion of the procedure by and by updating the CTS. If the SPC, package insert and labelling are changed as a result of the procedure, the updated SPC in English is attached to the end of procedure , from the RMS. The MAH should send an updated version of the SPC in the national translations (where necessary) and electronic version in Word of all product literature text affected, within 10 working days after the date of approval of the variation. Competent authorities should implement the

7 Page 7 of 10 decision nationally within 30 days after receiving the final approved translations of the SPC, package insert and labelling where applicable in their national languages. All competent authorities should maintain CTS and ensure that the information of each veterinary medicinal product is updated. The RMS is responsible for sending any revised SPC to the the VMRI database. 5.7 Referral If any CMS is unable to agree with the decision of the RMS within the time period mentioned (Day85), the matter shall be referred to arbitration according to Article 39 (2) of Directive 2001/82/EC as amended, by those CMS which are against the opinion of the RMS. In case of a refusal of the variation application by both the RMS and the CMS, the MAH may refer the matter to the CVMP for arbitration within 10 days of the end of the procedure.

8 Page 8 of 10 ANNEX I Time tables for Type II variations

9 Normal procedure for Type II variations Day 0 Day 40 Day 55 Day 59 Clock off period Day 60 Day 85 Day 90 Start of the procedure, RMS notifies the time table to the CMS by CTS and (MRVE mailbox) and to the MAH by RMS circulates the PVAR and draft decision to the CMS and to the MAH CMS send any comments on the PVAR and draft decision to the RMS and the MAH RMS sends any RSI to the MAH and the CMS, clock stop Should not be longer than days (60 days for the MAH to provide the responses and 60 days for the RMS to prepare the FVAR) Restart of the procedure. RMS circulates the FVAR and (revised) draft decision to the CMS and to the MAH CMS send final decision on the variation to the RMS and MAH End of the procedure, the RMS notifies the completion of the variation procedure and the outcome to CMS and MAH.

10 Page 10 of 10 Extended procedure for Type II variations Day 0 Day 70 Day 85 Day 89 Clock off period Day 90 Day 115 Day 120 Start of the procedure, RMS notifies the time table to the CMS by CTS and (MRVE mailbox) and to the MAH by RMS circulates the PVAR and draft decision to the CMS and to the MAH CMS send any comments on the PVAR and draft decision to the RMS and the MAH RMS sends any RSI to the MAH and the CMS, clock stop Should not be longer than days (90 days for the MAH to provide the responses and 60 days for the RMS to prepare the FVAR ) Re-start of the procedure. RMS circulates the FVAR and (revised) draft decision to the CMS and to the MAH CMS's send final decision on the variation to the RMS and the MAH End of the procedure, the RMS notifies the completion and the outcome of the procedure to CMS and MAH.