Established medicines: marketing authorisation application changes
Source: gov.uk (2025-04-01)

Details of the process changes for established medicines, effective from 1 March 2024, which apply specifically to chemical products.

Changes to the marketing authorisation application process

1. From 1 March 2024, new process changes are being introduced for applications for marketing authorisations for established medicines. The scope of established medicines includes products that are not new active substances or line extensions to new active substances. These process changes apply specifically to chemical products. Biosimilars are excluded.

2. These changes are in addition to measures already implemented:

a. Eligible national marketing authorisation applications (MAA) submitted before 1 January 2024, awaiting first assessment, may convert to the Mutual Recognition and Decentralised Reliance Procedure (MRDCRP) (https://www.gov.uk/guidance/decentralised-and-mutual-recognition-reliance-procedure-for-marketing-authorisations) or European Commission Decision Reliance Procedure (ECDRP) (https://www.gov.uk/guidance/european-commission-ec-decision-reliance-procedure).

b. Checklists (https://www.gov.uk/guidance/apply-for-a-licence-to-market-a-medicine-in-the-uk#checklists---established-active-substance-maas) are available to support applicants to complete right-first- time submissions.

c. The most common application flaws, where we frequently raise deficiency points, are:
- bioequivalence issues and inappropriate use of biowaivers
- product specifications, appropriateness of dissolution methods and limits, and impurities test and limits including the requirement for an assessment of nitrosamines content
3. We will take the approaches set out below for all applications until further notice, and have reviewed them and made changes clarified in this guidance after three months:
- Revised process for applications received and where assessment has not started (#revised-process-for-applications-received-and-where-assessment-has-not-started)
- Revised process for applications which are already under assessment or have received a request for further information (#revised-process-for-applications-which-are-already-under-assessment-or-have-received-a-request-for-further-information)
4. The main changes are as follows:

a. we will not process incomplete applications (see 1.6.2)

b. we will only send one request for further information (RFI) (see 1.6.5)

c. following approval, we will ask applicants to submit a template prepopulated with the lay summary for the UK public assessment report (UKPAR) (see section 3)

5. We are committed to being transparent about our performance in reaching regulatory decisions on each type of fully compliant application. We publish these data on our website each month – see the latest performance data (https://www.gov.uk/government/publications/mhra-performance-data-for-assessment-of-clinical-trials-and-established-medicines).

6. Likewise, we are committed to providing applicants with information and support. Our Regulatory Information Service (RIS) acts as the single main point of contact for marketing authorisation holders of medicines and their representatives.

Telephone (weekdays 9am to 5pm): xx-xxxx-xxxx

New licence applications: xxx@xxx.xx (mailto:xxx@xxx.xx)

1. Revised process for applications received and where assessment has not started

1.1. Prior to assessing an application, we will do our best to notify the applicant (by email) of our intention to begin assessment of their MAA.

1.2. We ask that all applicants, irrespective of this notification, provide the following documentation (by means of a new eCTD sequence via the MHRA submissions portal in MS Word rather pdf) as a matter of urgency:

a marked-up comparison of the summary of product characteristics (SmPC), if applicable
- a comparison of the text in the patient information leaflet (PIL) against the equivalent product information for the reference medicinal product (where appropriate)
- any additional stability data that supports an increase in shelf life since the original submission, and any updates to relevant documents to reflect this
1.3. Applicants will have the opportunity to provide updated GMP certificates and/or QP declarations at this time.

1.4. If the applicant considers that they have not submitted the complete documentation required to support their application, or they do not wish to have their application processed as described below under 1.6, they will have the opportunity to withdraw their licence application before assessment has started and receive a 90% refund of the application fee.

Find out more about the fees we charge at MHRA fees (https://www.gov.uk/government/publications/mhra-fees/current-mhra-fees).

1.5. Once assessment of an application has commenced, as detailed under 1.6 of the process below, if it is subsequently withdrawn by the applicant before determination, any refund on withdrawal will depend on the stage in the assessment process that has been reached in line with The Medicines (Products for Human Use) (Fees) Regulations 2016 (as amended).

1.6. From 1 March 2024, the assessment process is as follows:

1.6.1. When we begin the assessment, we will carry out a technical completeness check of the application.

1.6.2. The application will be refused if it is determined that the data required by regulations 49 – 55 and Schedule 8 of the Human Medicines Regulations 2012 have not been submitted. Examples of this include incomplete documentation even where there are commitments given to provide pivotal data during the assessment procedure.

1.6.3. Applications which we consider technically complete will be scientifically assessed.

1.6.4. When taken together, if we consider deficiencies present a potential serious risk to public health, we will refer the application to the Commission on Human Medicines (CHM) for advice on refusal. In all cases where an application is referred to the CHM and their advice is to refuse it, a letter will be issued from the CHM, and the applicant will have the usual appeal rights as described in paragraph 6 of Schedule 11 of the Human Medicines Regulation 2012 (as amended).

1.6.5. In other cases, where there are deficiencies, the applicant will receive a request for further information (RFI). Note: there will no longer be more than one RFI and, for some of these applications, we will no longer issue an assessment report alongside the RFI.

1.6.6. Applicants will have a maximum of 60 calendar days to respond to this request. The RFI letter will include a contact email for questions or clarifications on the questions raised.

1.6.7. There will be three possible outcomes beyond this point:

1.6.7.1. If the response submitted within 60 days is complete and satisfactory and, where necessary, updated documentation has been provided to respond to all the questions raised in the RFI, including questions on the product information, the application will be determined as approved in line with Regulation 58(4).

1.6.7.2. If the response is incomplete or does not resolve the issues raised on quality, safety, or efficacy, we will refer the application to the CHM for advice on refusal.

1.6.7.3. If we do not receive a response within the timeline of 60 days, we will refer the application to the CHM for advice on refusal.

1.6.8. We will not grant extensions to response times. We will review exceptional circumstances to meet public health needs and minimise the impact on patients on a case-by-case basis.

2. Revised process for applications which are already under assessment or have received a request for further information

2.1. For all applications currently under assessment or which have been issued with an RFI, we will limit applications to one further final RFI.

2.2. If within the 60-day timeframe following the date of the final RFI, we have not received a response, or if we have not received sufficient evidence of safety, quality and efficacy to be able to approve it, we will refer the application to CHM for advice on refusal on the grounds that safety, quality or efficacy have not been demonstrated in line with Regulation 58(4).

2.3. Once we have assessed the response to the final RFI, we will make a decision on approval or refusal using criteria detailed above under 1.6.7.

3. UK public assessment reports (UKPAR)

3.1. For each of the two processes described above, following an assessment decision to approve, we will ask applicants to provide a template prepopulated with the Lay Summary for the UK Public Assessment Report (UKPAR).

3.2.Templates are available at Apply for a licence to market a medicine in the UK (https://www.gov.uk/guidance/apply-for-a-licence-to-market-a-medicine-in-the-uk#uk-public-assessment-report-ukpar-templates). The applicant should use the template that corresponds to the legal basis of their application.

3.3. We will complete the draft UKPAR supplied by the applicant and publish it on the MHRA Products website (https://products.mhra.gov.uk/).

3.4. Where necessary, before the publication of the final public assessment report, we will consult marketing authorisation holders further on the text of the final public assessment report.

Published 28 February 2024