What Are The Steps To Consider In a Repeat Use Procedure?

In this article, we look at the issue of Repeat Use Procedure. We give an overview and consider some of the issues that need to be addressed during the process.

What Is A Repeat Use Procedure?

According to the CMDh the ‘Repeat Use Procedure’(RUP) is the use of the Mutual Recognition Procedure (MRP) after the completion of a first MRP or Decentralised Procedure (DCP) for the recognition of a marketing authorisation by other Member States (MS).

This means that a marketing authorisation holder may use the MRP several times for the same marketing authorisation, once the first MRP is complete, to include additional member states (MS) that were not involved in the initial MRP.

For the initial MRP the Reference Member state (RMS) leads the administrative procedure and also prepares the Assessment Report (AR) which summarises the dossier and critically evaluates the safety, efficacy and quality of the medicinal product. This AR is made available to all Concerned Member States (CMS) by the RMS and the CMS then base their evaluation of the dossier on the AR, for this reason the dossier submitted to all of the member states must be identical. The MS have 90 days to accept the AR from the RMS and issue a marketing authorisation or if a ‘potential serious risk to public health’ is identified by a CMS the application will be sent for further discussion to the Coordination Group for Mutual Recognition and Decentralised Procedures (CMD(h)). If the issue is not resolved within 60 days, the application is then sent to the CHMP for arbitration.

Steps To Consider In a Repeat Use Procedure

Prior to beginning a repeat use procedure, the MAH should:

  1. Ensure that all ongoing procedures are finalised:

  • Changes in RMS post-MRP
  • Withdrawal of the application during an earlier procedure
  • Variations
  • Harmonisation of labelling and package leaflet
  • Renewals
  • Updating of the dossier
  • Repeat use of ‘old Dossiers’
  1. Approximately 90 days before the submission, send a written request for the Repeat Use Procedure to the RMS and agrees a date of submission.

The RMS then writes an addendum to the original AR commenting on the changes made subsequently.

14 days before the procedure is scheduled to start the MAH submits the application to the ‘New’ CMS according to Article 28(2) of EC Directive 2001/83 and the RMS circulates the updated AR to the CMSs.

The repeat use procedure is between the RMS and new CMS only and no changes are permitted during the procedure.

Dossier Issues To Be Aware Of

The dossier submitted must comprise of:

  • the original dossier updated by any variation or renewal which has been approved or amended after authorisation.
  • A proposal for the SPC, PIL and labelling which should be identical to the currently authorised version.

The new CMS will validate the application as per the CMDh procedure for automatic validation of MR Procedures for new applications.

Frequent Validation Issues

Some Frequent issues found on validation are:

  • Old dossiers may not always meet the meet updated guidelines/legislation example, pharmacovigilance.
  • Incomplete variations, renewals.
  • Legal basis issues
  • Expired certificates example, CEP/GMP

Provided there are no issues during the validation of the submission the procedure is started (day 0). All CMSs must send their comments to the RMS, CMS and applicant by day 30 and the applicant must respond to any queries by day 40. An evaluation of the responses is issued by the RMS by day 48. Any remaining comments are circulated by the CMS to the RMS and applicant by day 55. During days 55-59 the applicant and the RMS will communicate and clarify if the procedure can be closed at day 60 or if there is a requirement for further responses.

Following a successful procedure, the new CMS must recognise the MA of the product with the same SmpC. Labelling and package leaflet (PIL) that were approved in the previous MRP or DCP. However, the PIL must be updated at the end of the procedure to include the product names and the new CMS in section 6.

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