Renewal of licences

Under the new medicines legislation which was implemented on 30 October 2005, marketing authorisations (MAs) will be valid for five years and then may be renewed on the basis of a re-evaluation of the risk-benefit balance. Once renewed, the marketing authorisation will be valid for an unlimited period unless there are justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal. In addition, the five-yearly cycle of Periodic Safety Update Reports (PSURs) with renewal has been replaced by a three-year cycle.

Guide to making an application for renewal of a marketing authorisation
Guidelines on the processing of renewals in the centralised and mutual recognition/decentralised procedure are available on the EMEA and Heads of Agencies (CMD (h)) websites. These guidelines contain details of the new requirements and should be consulted as appropriate.

In summary, renewal applications under the new legislation should consist of the following information:

• administrative details including cover letter and application form, details of QP for Pharmacovigilance, contact person for defects and recalls and contact person for information
• list of all post-authorisation submissions since authorisation/last renewal
• follow up measures/specific obligations
• certificate of compliance with Good Manufacturing Practice (GMP) and QP declaration that the active substance is manufactured in accordance with GMP
• product information-Summary of Product Characteristics (SPC), leaflet and label
• quality overview (quality expert statement), together with the CV of the expert
• clinical overview (clinical expert statement), together with the CV of the expert
• reports of post-marketing experience (PSURs)
• SPC, labelling and patient information leaflet (the SPC must be submitted as a word document (*.doc) using the Word template as specified within special Mail 5 - section 3.4 and section 4.7)

The renewal application should be submitted according to the EU Common Technical Document (CTD) format.

Timing of submission
Under the new legislation applications for renewal should be submitted at least six months before expiry.

Requirements for marketing authorisations which have been renewed prior to 30 October 2005
A further renewal under the new legislation will be required for products authorised through the mutual recognition and centralised procedures. The UK does not require submission of further renewal applications for nationally authorised products that have been renewed at least once before 30 October 2005.

The periodic safety update report (PSUR) data should still be submitted. The PSUR data together with any PSURs previously submitted should cover the period since the last renewal. Where the period is covered by two or more reports a Summary Bridging Report covering all the PSURs (even those already submitted) should be submitted. Previously submitted PSURs need not be re-submitted provided that a listing of the original submission dates is appended to the summary bridging report but these reports should be available on request.

The format and content of the PSUR is outlined in the EU Pharmacovigilance Rules (see related links).

When submitting a PUSR in place of a renewal application for national MAs, please state clearly the submission is in place of a renewal application and state the date of last renewal. If there has been a Change of Ownership please give details of the renewal of the previous licence.

Cancellation
If the MA holder does not wish to renew the licence, a letter should be sent indicating the cancellation to:

Administrative Support Team
Medicines and Healthcare products Regulatory Agency
151 Buckingham Palace Road
London
SW1W 9SZ


Application form
An application for renewal of a marketing authorisation must be made using the following form:

EU form, application for renewal of a marketing authorisation (159Kb) 

This form is also available from the website of the EU Commission and should be used for all European and national renewal applications.
 

Fees
No fee is charged for the renewal of marketing authorisations except where UK is the eference Member State (RMS) for a product authorised via Mutual Recognician Procedure (MRP)/Decentralised Procedure (DCP). In the case of major applications (new active substances) a fee of £10,465 is payable for the first renewal only. For all other situations a fee of £807 is payable.
 

Submission of documentation
Each application must be accompanied by all relevant documents together with the application form in order for it to be validated. A covering letter listing the documents submitted should also be included.


Common renewal dates
Requests to bring forward a renewal date for one or more products in order to synchronise the renewal dates for a range of product strengths are generally facilitated. Any such proposal should be agreed with the Agency in advance of the proposed date and requests should, in the first instance, be directed to the Therapeutic Reviews Group via e-mail at: TherapeuticReviewsGroup@mhra.gsi.gov.uk

Products authorised nationally – BROMI Procedure
Following a successful BROMI project new procedures have been put in place for national renewals. This involves a reduced submission whereby information that is currently held on the Sentinel database may be omitted from the consolidated renewal file (see list below). In addition applicants are required to submit a cover letter which includes a checklist. This will enable us to channel the renewal application to the appropriate assessment team and expedite assessment. You should submit your national renewal through the portal in the usual manner and include the completed letter template (see link). The following documents may be omitted from the consolidated file if they are the same as previously advised and no changes are proposed:

• Details of contact persons
• Chronological list of variations
• Current Summary of Product Characteristics, labels and leaflets
• Authorisations/GMP Certificates for manufacturing sites
• Declaration from a QP that the active is manufactured in accordance with GMP.

You are expected to check the information held on RAMA. Please note that details of any errors or anomalies that you may identify in the licence data held on our systems should be sent to the Data Review Team at DataReviewTeam@mhra.gsi.gov.uk. If you do not have access to RAMA please submit the documents but still use the letter template.

BROMI Renewal Letter Template (46Kb)

Products authorised nationally
For national UK MAs which have not been renewed prior to 30 October 2005, the guideline on processing renewals in the MR/decentralised procedure should be followed for documents to submit.


Products within the Mutual Recognition procedure
The application should be submitted to all Member States involved in the procedure at the same time. Flexibility will be maintained in setting the common renewal date. However, the principle applies that the renewal application can be submitted for a renewal date earlier than five years but this must not extend beyond five years. Submission of the renewal should therefore be based upon the earliest renewal date in any one Member State unless an alternative date has been agreed (please consult the guidelines).


Products within the Centralised Procedure
The same general principles apply to the submission of renewal applications for products authorised through the Centralised procedure. The European renewal application form should be completed as for other applications (please consult the guidelines for further information).

Contact for further information
For further information about Renewal applications please telephone the Regulatory Information Service (RIS) on 020 3080 7400 or email Therapeuticreviewsgroup@mhra.gsi.gov.uk

FAQ for renewals
Q1. I have a national MA which has been renewed previously what submission should I make
A. A PSUR submission should be provided. The PSUR can be accompanied by a Clinical expert statement. If any changes to the product information are identified on preparing the PSUR these should be made by variation. You should not wait for confirmation from the MHRA that the changes are required and the variation should be submitted as soon as possible following the submission of the PSUR.

Q2. We have a mutual recognition MA which has been renewed previously prior to 30 October 2005. Does this require a further renewal?
A. Yes, all MR products must undergo a further renewal following the introduction of the new legislation.

Q3. We have an MR product where only the UK is involved. Does this now follow national guidelines?
A. No, once an MA has been through mutual recognition the MA remains mutually recognised regardless of how many member states are involved in the procedure.

Q4. We wish to apply for a change of ownership for a MA but there is still an outstanding renewal what should we do?
A. While there is no legislative requirement to complete renewals prior to a change of ownership we will make every effort to complete these before the change of ownership. Please give sufficient notice of your intent to change ownership to help us achieve this.

Q5. We are taking ownership of an MA which still has a pending renewal what do we do?
A. Under the BROMI initiative pending renewals will be transferred to the new MA. Please ensure that you have copies of the data supplied. Updates to product information will not be allowed for these applications and you should submit your new livery labels and leaflets to the Patient Information and Quality (PIQ) department for assessment prior to marketing. Please note that new leaflets must be supported by an appropriate user acceptance test or bridging report. Please contact the PIQ department for details.

Copies of valid Good Manufacturing Process (GMP) certificates should also be supplied for the renewal application and an updated PSUR should also be supplied. Please ensure you state clearly on the cover letter that this information is to be attached to a pending case folder and is not a new application.

Q6. We have a MA from a change of ownership. It is a national MA which has been renewed previously. Do we need to submit a further renewal on the new MA.
A. No. The previous renewal is still valid. You should ensure you know when the next PSUR is due to comply with the legislation. Please remember the dates for PSURs submissions are based on the data lock point of the previous PSUR and not on date of grant. Please see the PSUR page of our website for further information.

Future developments
Better Regulation of Medicines Initiative (BROMI) As part of our better regulation initiatives a pilot study with RAMA XL companies has recently taken place whereby information that is currently held on the Sentinel database may be omitted from the consolidated renewal file (for example, the list of approved licence variations). In addition applicants will be required to submit a short questionnaire on whether any safety issues have been identified in the Periodic Safety Update Report (PSUR) requiring amendment to the reference safety information and product information. This will enable us to channel the renewal application to the appropriate assessment team and expedited processing.

Better Regulation of Medicines Initiative (BROMI): Fourth report on progress (182Kb)