Co-ordination Group for Mutual Recognition and Decentralised Procedures - Veterinary EMEA/CMD(v)/115405/2005 BEST PRACTICE GUIDE for Type IB Variations Edition 00 Edition date: 10-12-2005 Implementation date: 01-01-2006 EDITION DATE PAGE/S REASON FOR CHANGE 00 10/12/05 all General update of document VMRF/117/03 final to take into account experience and Directive 2001/82/EC as amended by Directive 2004/28/EC 01 02
for Type IB Variations Page 2 of 11 Index 1. Introduction 2. Aim and Scope 3. Reference documents and/or related documents 4. General 5. Type IB Notification procedure: 5.1 Pre-submission phase 5.2 Submission phase 5.3 Validation 5.4 Start of notification procedure 5.5 Evaluation procedure 5.6 Outcome of the notification procedure 5.7 Referral Annex I Examples Acknowledgement of a valid type IB notification Refusal of type IB notification
for Type IB Variations Page 3 of 11 1. 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 IB minor 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 IB 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. - Guideline on dossier requirements for Type IA and Type IB notifications (NTA Volume 6C). 4. GENERAL As a result of the replacement of the Variation Regulation (EC) No 541/95, as amended by Regulation (EC) No 1146/98 and by Regulation (EC) No 1084/2003 of June 27, 2003, two categories of minor variations, the Type IA and Type IB Notification procedures are
for Type IB Variations Page 4 of 11 introduced. In Annex I of the revised Regulation the categories of changes are listed, and conditions that must be fulfilled are set out. For Type IB notifications, 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 http://pharmacos.eudra.org/f2/eudralex/vol-6/home.htm#6c and additionally national application form if necessary. For validation and acceptance of notifications of Type IB, documentation to demonstrate compliance with the conditions set out in Annex I of the Regulation EC/1084/2003 must be submitted. In order to clarify what documentation should be submitted with these notifications, the Commission has published a Guideline on dossier requirements for Type IA and Type IB notifications in the Notice to Applicants, Volume 6C. See also Notice to Applicants, Volume 6A, Chapter 5. If a notification requires consequential revision of the Summary of Product Characteristics, label and package insert, as mentioned in Article 5 of Regulation (EC) No 1084/2003, it is the responsibility of the MAH to submit these documents, where necessary. The notifications 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. 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.
for Type IB Variations Page 5 of 11 5. TYPE IB NOTIFICATION PROCEDURE 5.1. Pre-submission phase The MAH will contact the RMS at least 7 days prior to submission in order to obtain the Type IB notification procedure number. The MAH may discuss with the RMS, in case of doubt, the variation type number and subcategory. The MAH will insert this Type IB notification 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 e-mail via MRVE mailbox. 5.2. Submission phase The MAH will submit simultaneously to the RMS and CMS the following: The variation application form with MR notification number completed on page 1. Index of the submitted documentation including conditions specified for the proposed change(s) and corresponding supporting documentation as listed in the Commission Guideline on dossier requirements for Type IA and IB notifications. This could be directly copied or printed from the Guideline. The MAH should send an e-mail identifying the procedure (name of the product and type IB procedure 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 e-mail with the relevant information to the CMS. In the case of more than one change to be made the MAH must submit the appropriate application for each change, at the same time and clearly describe the relation between all these variations.
for Type IB Variations Page 6 of 11 To be valid an application shall be consistent with the provisions of paragraphs 1 to 4 of Article 4 of the Regulation and with the conditions set out in Annex I. RMS should send an e-mail to CMS and MAH with the proposed timetable/s. 5.3. Validation To be valid an application shall be consistent with the provisions of paragraphs 1 to 4 of Article 5 of the Regulation and with the conditions set out in Annex I. CMS should comment on the validity of the variation in respect of the application form (English and national language where relevant) and the submitted documentation. CMS should indicate on the CTS record and by e-mail (with the reasons) within 5 working days after the receipt of the list of dispatch dates if the application is invalid. If the application is considered valid the CMS will complete CTS. 5.4. Start of notification procedure (Day 0) If the RMS receives no notification of an invalid application the RMS acknowledges the receipt of a valid notification and starts the notification procedure. The RMS informs the CMS and MAH by email about the start date (Day 0), which is normally 5 working days after receiving the list of dispatch dates and completes the CTS record. 5.5. The Evaluation Procedure (Day 0 to Day 30) According to the Regulation (EC) No 1084/2003 the evaluation of the change applied for is the responsibility of the RMS. This implies that the RMS may ask the CMS for input where this is needed for his decision. This situation will occur for the following two types of changes applied for: Change in the name of the veterinary medicinal product (in a CMS) (No 2 of Annex I); Change in pack size (No. 41a2 and No 41b of Annex I). If there are objections from CMS regarding the change applied for, it is the responsibility of
for Type IB Variations Page 7 of 11 the CMS to notify this comment to the RMS and the Applicant, within 20 calendar days following the start of the procedure. Within 30 days of the start of the procedure the RMS shall assess the notification and send its opinion, taking into account the comments received. 5.6. Outcome of the notification procedure The RMS comes to a decision about the outcome of the procedure by Day 30. The following opinions are possible: Acceptance: By day 30 the RMS informs the MAH and CMSs by e-mail via MRVE mailbox that the notification is accepted, together with the date of approval. If the SPC, package leaflet and labelling are changed as a result of the procedure, the updated SPC in English is attached to the Day 30 e-mail 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 decision nationally within 30 days after receiving the final approved translations of the SPC, package leaflet and labelling where applicable in their national languages. Non-acceptance: By day 30 the RMS informs the MAH and the CMS by e-mail about the deficiencies ( Notification With Grounds ) of the notification and stops the clock for the procedure. If the MAH wishes to respond, the response must be submitted within 30 days to RMS and CMS with the list of dispatch dates. If the MAH takes due account of the grounds set out in the opinion, the RMS re-starts the procedure (normally within 5 days of the reception of the list of dispatch dates) when all CMS have received the amendments. The RMS informs MAH and CMS about the procedure re-start and the new 30 days timetable by sending an e-mail. By the new day 30 the RMS concludes the procedure either as accepted (see above) or refused and informs
for Type IB Variations Page 8 of 11 MAH and CMS of its decision. Examples of suitable texts to be used for letters about the notification outcome issued to the MAH on completion of the process are provided in Annex 1. 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 VMRI database. 5.7. Referral Within 10 days of receipt of the decision of a non-acceptance of the procedure the MAH or the CMS may refer the matter to the CVMP for arbitration.
for Type IB Variations Page 9 of 11 ANNEX 1
for Type IB Variations Page 10 of 11 Sample text for inclusion in the approval or refusal notifications issued to the MAH on completion of the procedure: Example 1. APPROVAL OF TYPE IB NOTIFICATIONS Product Name Procedure Number Start Date The <<competent authority>> agrees to the request to vary the Marketing Authorisation detailed in the application. The proposed change is: << enter specific change applied for>> The application is approved on <<date>>. Example 2. REFUSAL OF TYPE IB NOTIFICATION Product Name Procedure Number Start Date The <<competent authority>> cannot accept the Type IB Notification << enter specific change applied for by notification>> The notification is considered invalid because of the following: <<enter reasons for non-acceptance>