MHRA publishes guidance on new marketing authorisation assessment routes

The assessment runs in two phases totalling 150 days with a 60-day clock off period between phases if needed. The first assessment phase will be completed 80 days after the clock starts. Any issues arising during the first phase will be raised with applicants in a "letter requesting further information" (RFI letter). These issues should be addressed within the clock off period. The guidance states that requests to extend the clock off period for up to a further 60 days "may be granted only for exceptions". Phase I assessment will also address eligibility for grant of orphan status.

The second phase of the assessment will start once the applicants' responses are received. The MHRA will operate a 'fixed submission date' system to facilitate consultation with the Commission on Human Medicines (CHM). The guidance recommends that applicants contact the MHRA Assessment Team ahead of their intended date of response submission to align with the CHM's meeting schedule.

For new active substances and biosimilar products, the guidance describes:

For existing active substances applications, the guidance refers applicants to the MHRA guidance on Reference Medicinal Products for applications made only to GB. Applicants are also advised to consult any MHRA product-specific bioequivalence guidance for applications made only to GB.

For both new active substances and biosimilars and existing active substances, the guidance describes the content and format of documents that make up a valid application or dossier. These include common technical (CTD) modules 2-5 and a UK specific CTD module 1, the summary of product characteristics and patient information leaflet and, if applicable, an active substance master file. Applications must also include a cover letter. The cover letter should detail the intention to seek orphan status or an MA under exceptional circumstances, as applicable. Applications should be submitted via the MHRA Submission Portal.

Assessment of the first module will start from Day 0 with the assessment cycle being completed within 60 days. Following each assessment cycle, a Module Assessment Summary (MAS) will be issued by Day 60. The MAS enables the applicant to update the module, and the updated modules should be included in the final phase.

The final phase should be completed within 100 days in two stages with a clock off period after 60 days. The MHRA may issue an RFI by Day 60 and applicants will be able to discuss any issues identified in the RFI with the MHRA within 30 days. The clock then resumes on Day 61 with the final decision on approvability reached by Day 100. Orphan status will be determined at the time of grant of the MA.

The MHRA has stated its aim to determine GB MAs under the ECDRP as soon as possible and suggested that a delay in submission may affect the 67-day timeline. There is the possibility that the MHRA may make major objections or require significant amendment of the product information, which will move the application on to the standard national procedure timetable. But the MHRA has stated that this would be rare. The guidance also states that points of clarification (for example, relating to an incomplete dossier or missing assessment reports) may cause delays.

The timetable is different depending on when the application is made in relation to the EMA's Committee for Medicinal Products for Human Use (CHMP) opinion. If the submission is made within five days of the CHMP opinion, then a 67-day timetable applies from the date of the CHMP opinion (provided the EC decision has been received). If the application is made more than five days after the CHMP opinion, then the timetable starts on the date that the MHRA validates the application, and the MHRA has stated that determination may be delayed in this scenario.

The MHRA promises in the guidance to raise concerns about approvability at the earliest opportunity. It also states that issues identified during assessment will be communicated by Day 46 and the MHRA expects to be able to resolve those issues without affecting the overall 67-day timetable.

The guidance sets out what applicants must do to apply for a GB MA under the ECDRP. It also refers to a fee that applies to the application after receipt of the dossier.

An applicant must first have a GB MA (known as PLGB) number. The guidance recommends that, once a positive CHMP opinion is anticipated, applicants should submit a letter of intent including:

The guidance explains that an application for GB MA can be made to the MHRA any time after EU approval, but the MHRA's intention is that applicants submit their application immediately on receipt of a positive CHMP opinion. The application should be submitted to the MHRA as a single eCTD (containing the entire dossier, including responses to CHMP questions) using MHRA Submissions. The dossier is not required if it has already been submitted to the MHRA as part of a NI application and no changes are required. The applicant should also submit all iterations of the CHMP assessment reports and opinion for the initial centralised procedure application and any variations, as well as the proposed product information.

To apply for GB orphan designation, applicants will need to include a specific GB form in the eCTD. Where EU or UK paediatric requirements apply, information and documents relating to those requirements must be included in the eCTD along with a specific overview table.

Finally, applications must include a cover letter containing various information listed in the guidance (including the centralised procedure number, a list of assessment reports and details of compliance with paediatric requirements) and several declarations concerning the conformance of the ECDRP application to the Commission approval, and the related CHMP assessment and opinion, on which it is based.

The applicant is also required to confirm:

The MHRA has stated that the first-round assessment should be completed by Day 42, at which point an MA will be granted if no concerns are raised. The MHRA may raise an RFI which will stop the application timetable for up to 28 days. In the guidance, the MHRA has made the general promise that MAs will be granted within 67 days if there are no outstanding points at Day 65.

There is the possibility that the MHRA may make major objections, require substantial amendment of the product information, or raise concerns that remain outstanding at Day 65, which will move the application on to the standard national procedure timetable. The guidance also states that points for clarification (for example, relating to an incomplete dossier or missing assessment reports) may cause delays.

The guidance sets out what applicants must do to apply for a UK or GB MA under the MRDCRP. It also refers to a fee that applies to the application.

An applicant must first have a PL or PLGB number, as applicable. Then the applicant should submit the dossier as an eCTD using MHRA Submissions. The guidance emphasises that the submitted dossier should be the entire dossier approved under the mutual recognition or decentralised procedure in the EU, including responses to reference member state (RMS) and concerned member state (CMS) questions. The applicant should also submit all iterations of the RMS assessment reports and end of procedure documents for the initial EU application and any variations, as well as the RMS MA grant letter and the proposed product information.

To apply for GB orphan designation, applicants will need to include a specific GB form in the eCTD. Where EU or UK paediatric requirements apply, information and documents relating to those requirements must be included in the eCTD along with a specific overview table.

Finally, applications must include a cover letter containing various information listed in the guidance (including the relevant mutual recognition or decentralised procedure number, a list of any product information differences, a list of assessment reports and details of compliance with paediatric requirements) and several declarations concerning the conformance of the MRDCRP application to the EU or EEA member state approval on which it is based.

In the guidance, the MHRA has stated its intention to determine applications for recognition within 67 days of the MHRA's validation of the application, although the MHRA considers that the vast majority of GB MAs should be approved by Day 42 (after the first round of assessment). In the guidance, the MHRA states its view that issues identified during assessment should be resolvable within the 67-day timetable. There is, however, a small possibility that the MHRA may make major objections or require significant amendment of the product information, which will move the application on to the normal national timeline. The guidance also states that points for clarification (for example, relating to an incomplete dossier or missing assessment reports) may cause delays.

The guidance sets out eligibility criteria and details of what applicants must do to apply for a GB MA under the UAP.

The guidance explains that the UAP will be available if:

An applicant must first have a PLGB number. Then the applicant should submit the dossier as an eCTD using MHRA Submissions, although this is not required if the MHRA was sent the dossier with a NI application. The guidance emphasises that the submitted dossier should be the entire dossier approved under the relevant procedure, including responses to questions raised during those procedures. The applicant should also submit all iterations of the assessment reports and end of procedure documents for the initial UK or EU application and any variations, as well as the MA grant letter and the proposed product information.

To apply for GB orphan designation, applicants will need to include a specific GB form in the eCTD. Where EU or UK paediatric requirements apply, information and documents relating to those requirements must be included in the eCTD along with a specific overview table.

Finally, applications must include a cover letter containing various information listed in the guidance (including the NI procedure number, a list of assessment reports and details of compliance with paediatric requirements) and several declarations concerning the conformance of the UAP application to the NI approval on which it is based.