Marketing Authorisations Variations 2021 UK Guidance

by
MedicinesUK Post-Exit Guidance Notes [2020]
Guidance

Variations to Marketing Authorisations (MAs) from 1 January 2021

How the MHRA will process variations to Marketing Authorisations (MAs) from 1 January 2021.

Published 27 October 2020
From:
Medicines and Healthcare products Regulatory Agency

New rules for January 2021

The UK has left the EU, and the transition period after Brexit comes to an end this year.

This page tells you what you’ll need to do from 1 January 2021. It will be updated if anything changes.

For current information, read: Medicines: apply for a variation to your marketing authorisation

You can also read about the transition period.

The guidance describes the approach the MHRA intends to take to the processing of variations to marketing authorisations from 1 January 2021.

1. Variations Procedure

The procedures detailed under Chapter IIa of Variations Regulation (EC) No 1234/2008, which specifically applied to variations to purely national Marketing Authorisations, will be incorporated into UK law from 11pm on 31 December 2020, and as such continue to apply to both pending and new variations to purely national UK Marketing Authorisations, from 1 January 2021 and can be found in new regulation 65C and Schedule 10A to the Human Medicines Regulations 2012 (“HMRs”).

In addition, unless specifically highlighted under section 3, the current variations classification guidelines, which explains the type of variation (Type IA, Type IAIN, Type IB, Type II or Extension) to submit and, where relevant, the conditions to be met and any required supporting documentation, will continue to apply.

Any extension application should be submitted in accordance with the procedures for new Marketing Authorisations. The variations classification guidelines will continue to apply until the MHRA issues any revised guidance in the future.

The UK will recognise any Article 5 recommendation published by the Co-ordination group for Mutual recognition and Decentralised procedures – human (CMDh) before 1 January 2021. Any specific request from a Marketing Authorisation Holder (MAH), concerning the classification of a variation, which is still pending (no recommendation) on 1 January 2021 or is submitted after 1 January 2021 will need to be submitted directly to the MHRA, who will issue its own recommendation.

2. Variation of a UK marketing authorisation

All Marketing Authorisations authorised in the UK by the MHRA before 1 January 2021 will be national (UK). Any pending and new variations will therefore only be processed to conclusion after 1 January 2021 as national variations, where the relevant national procedures will be followed.

Northern Ireland protocol

Community Marketing Authorisations

Under the Northern Ireland Protocol, Medicinal Products authorised via the centralised route will be directly authorised for use in Northern Ireland. Any variations to these Marketing Authorisations will be centrally managed by the EMA in accordance with relevant procedures. A separate MA will not need to be issued by the MHRA for NI. If the same product is separately authorised in Great Britain a separate variation application will need to be submitted to vary that authorisation.

Products authorised under EU Decentralised or Mutual Recognition Procedures Under the Northern Ireland Protocol, Medicinal Products authorised via the MR/DC procedure, where Northern Ireland is specifically included will be authorised for use in Northern Ireland. In these cases, a UK MA in respect of NI will be issued by the MHRA. Any variations to these Marketing Authorisations will be managed as part of the specific MR/DC procedure, according to the relevant procedures laid down in the Variations Regulation (EC/1234/2008 as amended), where worksharing will also be possible. If the same product is separately authorised in Great Britain a separate variation application will need to be submitted to vary that authorisation.

2.1. Pending variations (no decision)

How variations that are pending (‘no final decision) on 1 January 2021 would be finalised:

Purely national Marketing Authorisations (not part of any worksharing procedure)

These will be processed to conclusion under the transitional provisions, using the same purely national procedures that were in place prior to 1 January 2021.

UK Marketing Authorisation covered under Chapter II of Regulation (EC) No 1234/2008 (variations to marketing authorisations granted in accordance with Chapter 4 of the 2001 Directive i.e. mutual recognition/decentralised variations (Type IA, Type IB or Type II)

and

Purely National Marketing Authorisations before 1 January 2021, but part of a Worksharing Procedure under Article 20 of Regulation (EC) No. 1234/2008 (Type IB or Type II)

For variations falling under either of these two scenarios, whether or not the UK was the Reference Member State/Reference Authority (lead) for the procedure, the variation will be processed to its conclusion as a purely national variation. Every effort will be made to ensure that relevant procedural time periods are observed. The ongoing assessment will take into account where in the overall procedure the application has got to on 1 January 2021. Therefore, any information previously obtained, and any assessment reported on before 1 January 2021 will be taken into consideration as part of the UK assessment process.

Action to take if the applicant does not wish to continue with the relevant variation as a national (UK) application

The applicant should notify the licensing authority in writing that they no longer want the application to proceed. A partial fee refund may be applicable in line with the current MHRA fees regulations.

2.2. Pending variations (decision made)

In the event that the UK is not the Reference Member State or Reference Authority for a variation procedure and a final decision has already been taken by the lead authority, but not finally processed in the UK before 1 January 2021, the MHRA will implement the agreed outcome of the procedure.

2.3. New variations submitted from 1 January 2021

All new variations submitted from 1 January 2021 will be processed as purely national variations, according to the same transposed procedures, as were in place prior to 1 January 2021. There will be no provision for worksharing.

Northern Ireland protocol

New variations submitted from 1 January 2021 to MAs issued as a result of Northern Ireland’s involvement in European procedures will be managed in line with the base procedures.

All other new variations will be processed as purely national variations, according to the same transposed procedures, as were in place prior to 1 January 2021. There will be no provision for worksharing.

3. Points to note for specific changes submitted from 1 January 2021

3.1. Change to finished product manufacturer

A change in finished product manufacturing site, including as appropriate primary and/or secondary packaging site should be submitted under the relevant sub-change code under B.II.b.1 and be suitably supported. This includes the submission of a copy of the relevant Manufacturing Authorisation or as appropriate a valid good manufacturing practice (GMP) certificate issued by the UK, or a GMP certificate (or equivalent document) from the competent authority of a country on the approved country for batch testing list (currently EEA Member States, Australia, Canada, Israel, Japan, New Zealand, Switzerland and the USA).

More information about batch testing including a list of approved countries for authorised human medicines from 1 January 2021.

Where relevant reference to the EudraGMP database will suffice.

3.2. Change to importer/batch release site/quality control site

A change in importer/batch release site and/or quality control site should be submitted under the relevant change code under B.II.b.2 and be suitably supported.

3.2.1. Importer/batch release

The change should be supported by including a copy of the relevant Manufacturing Authorisation or a valid GMP certificate issued within the last 3 years (as issued by the UK or a country included on the approved country for import list (currently EU/EEA Member States).

Where relevant reference to the EudraGMP database will suffice.

3.2.2. Quality control site

The change should be supported by including a copy of the relevant Manufacturing Authorisation or a valid GMP certificate (as issued by the UK or a country included on the approved country for batch testing list (currently EEA Member States, Australia, Canada, Israel, Japan, New Zealand, Switzerland and the USA). However, see separate guidance considering any specific exclusions.

Where relevant reference to the EudraGMP database will suffice.

3.3. Change of Marketing Authorisation Holder (MAH)

A change of MAH, such as from a company outside the UK to one established in the UK, cannot be done as a variation. That change requires the submission of a Change of Ownership application. It should be noted that from 1 January 2021 the MAH will have 24 months to comply with rules on establishment in the UK.

However, in the interim, the MHRA will require a contact in the UK. The MHRA will contact EU or EEA MAHs to ask for details of a UK contact.

A change to the name/address of the MAH can be submitted as a Type IA IN under change code A.1, provided that it is not a change to the legal entity.

3.4. Change to the location of the Pharmacovigilance Systems Master File (PSMF) or the Qualified Person for Pharmacovigilance (QPPV)

As the MHRA will no longer have access to the Article 57 database, any change to the QPPV or location of the PSMF should be submitted under change code C.I.8.a (Type IA IN), provided the conditions and documentation requirements can be fully met.

The QPPV for UK authorised products must be established in the EU or UK on day one, and the PSMF for UK authorised products must be accessible electronically from the UK at the same site at which reports of suspected adverse reactions may be accessed.

Further guidance on submission of pharmacovigilance system details will be published in due course.

3.5. Implementation of the outcome of referrals and procedures concerning PSUR or PASS

Where the procedure has been finalised before 1 January 2021, the outcomes in relation to any required variations will be processed based on the decision already taken. Depending on the nature of the required changes, the variations should be submitted under the relevant main change codes of C.I.3 or B.V.b (usually type IA). The actual submission category will depend on the specific nature of the required changes, taking into consideration if further assessment is required and its level.

From 1 January 2021, the MHRA will be carrying out our own assessments, the outcomes of these assessments will be published together with advice on implementation. Where a variation is required will usually be a Type IA.

3.6. Submission of protocols and study reports for post authorisation safety studies (PASS)

Although not actually variations, whether or not carried out in relation to a condition of the MA or voluntarily, the protocol and final study reports from safety studies should be submitted to the MHRA within 12 months of the end of data collection.

It has been decided that the most effective way of processing these is according to the Type II variations procedure, and they should be submitted under change code C.I.13. The submission should be accompanied by the appropriate fee, which is the same as that of a Type II or Type II complex variation. See also separate guidance on our approach to pharmacovigilance procedures from 1 January 2021.

3.7. Submission of paediatric study reports for assessment

From 1 January 2021, holders of a UK marketing authorisation who sponsor a paediatric study (which involves the use in the paediatric population of a medicinal product to which that authorisation relates), must submit the results of this study to the MHRA within the period of six months from the end of the study. MHRA has issued separate guidance setting out the submission requirements and procedures for assessment of completed paediatric studies. In cases where an initial appraisal indicates that an assessment is required, the MAH will be asked to submit the paediatric data as a Type II complex variation to MHRA under change code C.I.13.

If the results of a paediatric study have been submitted for assessment to EMA or CMDh under Article 46 of Reg.1901/2006/EC prior to 1 January 2021 MHRA will request MAHs to submit a Type IB variation to update the product information (PI) if there are proposed changes to the PI that can be directly implemented to relevant UK products following the completion of the EU procedure.

This guidance will apply from 1 January 2021 in line with the Human Medicines Regulations (Amendment etc.) (EU Exit) Regulations 2019.

Contact

For further information, please email our Customer Services Centre at info@mhra.gov.uk or call 020 3080 6000. Alternatively, contact your Trade Association by emailing:

Published 27 October 2020
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