Guidance

International Recognition Procedure

Updated 14 July 2026

Procedure developments will be introduced to enhance efficiency and better support applicants with the International Recognition Procedure process from 13 July 2026.

Key updates include:

• A single opportunity to respond to Validation Correction Requests (VCRs)
• Advance notice (8 weeks) required for new active substance submissions
• Reduction of the Route B reference approval window from 10 years to 5 years (Route A remains unchanged at 2 years)

A transition phase will be in place; therefore applicants can continue using the current process until 31 August 2026. Updated guidance reflects these changes.

These updates are expected to have minimal impact and are designed to improve clarity, efficiency, and predictability when planning submissions.

1. Overview

The International Recognition Procedure (IRP) was introduced on 1 January 2024. The IRP has been introduced to complement the National Pathway for products where applicants have already received an authorisation for the same product from one of MHRA’s specified reference regulators (RRs).

The same product is defined as having the same qualitative and quantitative composition (active substance(s) and excipients), the same pharmaceutical form and the same therapeutic use from Applicants belonging to the same company or group of companies or which are ‘licensees’. 

The applicant will need to demonstrate this by providing proof of approval alongside full unredacted assessment reports from the reference regulator to support their IRP application. Further details on supporting documentation can be found in Section 10

IRP allows the MHRA to take into account the expertise and decision-making of trusted regulatory partners for the benefit of UK patients. MHRA will conduct a targeted assessment, based on the unredacted assessment report issued by the reference authority but will still retain the authority to approve or refuse applications if the scientific evidence provided by the applicant is considered insufficiently robust.

2. Scope

IRP can be used for the following types of marketing authorisation applications (MAAs) according to the Human Medicines Regulations 2012 (HMRs):

• Regulation 50: chemical and biological new active substances and known active substances
• Regulation 51B: generic applications
• Regulation 52B: hybrid applications
• Regulation 53B: biosimilar applications
• Regulation 55: new fixed combination product applications

Following the implementation of the Windsor Framework on 1 January 2025, applications for GB MAs covering Great Britain only will no longer be possible.  All applications must be for UK-wide MAs.  Please refer to additional guidance on UK-wide licensing here: https://www.gov.uk/government/publications/uk-wide-licensing-for-human-medicines/uk-wide-licensing-for-human-medicines

In all cases of IRP applications, the RR authorisation must have undergone a full and standalone review. RR assessments based on reliance or recognition of authorisations in another territory cannot be used to support an IRP application. Full unredacted assessment reports from the referencing authority will be required to support the IRP application. It is the responsibility of the applicant to provide the requested documentation. It is not the responsibility of the RR to provide any documentation directly to the MHRA.

Conditional and exceptional circumstances MAAs (or international equivalent such as provisional or accelerated approval) can support an IRP application. Emergency approvals are not eligible.

IRP can be used for post-authorisation procedures including line extensions, variations and renewals (see Post-authorisation IRP application).

The following submission types are not within scope:

• Traditional herbal registrations
• Homoeopathic registrations (Simplified Registration Scheme)
• Homeopathic national rules authorisations (National Rules Scheme)
• Well-established use bibliographic applications (Regulation 54 of the Human Medicines Regulations)

Cancelled authorisations cannot be used to support an IRP application.

Additionally, applications that have previously been submitted via the national route and been refused by MHRA or withdrawn before determination cannot be resubmitted through IRP. The direct national route should be used clearly addressing the major objections or other concerns raised during the previous assessment.

In the instance that the MHRA advises that an application is not suitable for IRP, it can be submitted via the direct national route if MHRA requirements are met.

3. Reference regulators (RRs)

Acceptable RRs are shown in the table below.

Country or jurisdiction	Regulatory authority
Australia	Therapeutic Goods Administration (TGA)
Canada	Health Canada
Switzerland	SwissMedic
Singapore	Health Science Authority Singapore (HSA)
Japan	Pharmaceuticals and Medical Devices Agency (PMDA)
United States	Food and Drug Administration (FDA)
European Union/European Economic Area	European Medicines Agency (EMA) and Member State Competent Authorities of the EU, Norway, Iceland and Lichtenstein. (This includes approvals through the centralised, MRP/DCP and individual member state national routes)

4. Initial IRP marketing authorisation application (MAA)

There are two recognition timetables for initial applications (including line extension applications) through IRP:

• Recognition A: 60-day timetable
• Recognition B: 110-day timetable

The timetables are in calendar days.   

Suitability for Recognition A or B is determined by means of an eligibility form to be completed by the applicant 8 weeks before the planned date of MAA submission (see ‘How to apply’).

Applications that are determined not eligible for IRP can be submitted as direct national applications, if national requirements are met.

4.1  Key features of Recognition A

To be eligible for Recognition A, the RR approval must have been granted within the previous 2 years.

The manufacturing process must be the same as that approved by the RR, with evidence of compliance with Good Manufacturing Practice (GMP) meeting MHRA requirements at the time of IRP submission.

The Recognition route A will be open to applications that meet the criteria for IRP and do not trigger any of the Recognition B criteria (see below).

Recognition A procedures will run to a 60-day timetable starting from the date of successful validation.  There is no clock stop. If major objections or concerns are identified during the procedure which cannot be resolved within 60 days, the timetable will revert to Recognition B timeframe and the applicant will be notified.

4.2  Key features of Recognition B

To be eligible for Recognition route B, the RR approval must have been granted within the previous 5 years.

Authorisations more than 5 years old are not eligible for IRP.  Where there is an urgent public health need for a rapid assessment, a national fast track request is considered more appropriate in these circumstances: https://www.gov.uk/guidance/apply-for-a-licence-to-market-a-medicine-in-the-uk#fast-tracking-a-marketing-authorisation

IRP applications will follow Recognition B if any one (or more) of the following criteria applies:

• RR has granted a conditional or exceptional circumstances MA (or international equivalent)
• the application seeks a conditional or exceptional circumstances MA in UK
• additional manufacturing sites are cited that have not been assessed by the RR (except for secondary packaging, labelling and QP release sites)
• there are substantial changes in the manufacturing process or analytical methods compared to that assessed by the RR
• at least one manufacturing site is not yet GMP certified
• the environmental risk assessment (ERA) has not been assessed by the RR
• the risk management plan (RMP) as proposed for the UK has not been assessed by the RR
• there are UK-specific risk management activities (for example, which may be reflected as additional pharmacovigilance or additional risk minimisation activities)
• the RR has mandated one or more post-authorisation safety studies (PASS)
• the product contains a first-in-class new active substance
• clinical efficacy or safety data are available for a later cutoff than those assessed by the RR
• the pivotal clinical data are from single arm studies
• the pivotal clinical data include real-world data
• the product is an advanced therapy medicinal product (ATMP) as classified by the Human Medicines Regulations (as amended)
• the product is a fractionated plasma product
• the application includes a proposal for orphan drug designation
• comparator product used in bioequivalence or therapeutic equivalence study was sourced outside the UK/EU/EEA (generic/hybrid/biosimilar applications)
• product is not subject to medical prescription
• co-packaged medical device components are not already CE or UKCA marked (or self-certified where appropriate)
• where an IVD is required for correct use, the IVD is not CE or UKCA marked
• an approved body or notified body report is not available for integral medical device components
• the RR assessment cites or relies on guideline(s) that are not adopted by MHRA
• proposed container closure system (including pack sizes), shelf life or storage conditions differ from those accepted by the RR and/or additional stability studies have been provided to MHRA
• the product includes an excipient not previously used in authorised medicinal products in the UK.

Following successful validation, all recognition B procedures will run to a 110-day timetable in line with the procedure start date in the table below. This allows for consultation with the Commission on Human Medicines (CHM) if necessary.

Latest submission dates recommended for Recognition B applications to align with CHM dates are below. Corresponding procedure start dates and day 70 dates are also shown. 

Recognition B includes one clock stop at day 70, allowing the applicant up to 60 days to respond to any issues identified. If there are outstanding major objections or other concerns at day 110, formal advice on approvability will be sought from CHM, and the timetable will revert to the national 210-day timetable.

Submission deadline	Procedure start date	CHM meeting	Day 70
08/01/2026	22/01/2026	27/03/2026	02/04/2026
05/02/2026	19/02/2026	24/04/2026	30/04/2026
05/03/2026	19/03/2026	22/05/2026	28/05/2026
09/04/2026	23/04/2026	26/06/2026	02/07/2026
14/05/2026	28/05/2026	31/07/2026	06/08/2026
11/06/2026	25/06/2026	28/08/2026	03/09/2026
09/07/2026	23/07/2026	25/09/2026	01/10/2026
12/08/2026	26/08/2026	29/10/2026	04/11/2026
09/09/2026	23/09/2026	26/11/2026	02/12/2026
30/09/2026	14/10/2026	17/12/2026	23/12/2026
04/11/2026	18/11/2026	21/01/2027	27/01/2027
02/12/2026	16/12/2026	18/02/2027	24/02/2027
30/12/2026	13/01/2027	18/03/2027	24/03/2027
3/02/2027	17/02/2027	22/04/2027	28/04/2027
03/03/2027	17/03/2027	20/05/2027	26/05/2027
31/03/2027	14/04/2027	17/06/2027	23/06/2027
05/06/2027	19/06/2027	22/08/2027	28/08/2027
30/06/2027	14/07/2027	16/09/2027	22/09/2027
04/08/2027	18/08/2027	21/10/2027	27/10/2027
01/09/2027	15/09/2027	18/11/2027	24/11/2027
29/09/2027	13/10/2027	16/12/2027	22/12/2027

4.3 Extensions to a Route A or Route B timetable

Please note that the MHRA reserves the right to extend the timetable and switch the clock off during a procedure if deemed necessary. The applicant will be notified if this occurs.

The Route A  or Route B timetable may be extended in the following circumstances:

• If a second Request for Further Information (RFI) needs to be issued
• If the applicant requires additional time to respond to an RFI, and the MHRA agrees that an extension is appropriate. The regulatory clock will restart only once a complete response to all RFI questions has been received.
• If a Route A application requires referral to the Commission on Human Medicines (CHM) or if a Route B application requires a second consultation with CHM.

Each extension will be considered on a case-by-case basis, and the applicant will be notified prior to key determination milestones (Day 60 for Route A and Day 110 for Route B).

Please note, failure to address all questions may result in refusal of the application. If, during assessment, the MHRA determines that additional studies are required to support the application, it may conclude that the application is no longer eligible for the International Recognition Procedure. In these circumstances, the MHRA may request that the applicant withdraw the IRP application and resubmit it under the appropriate national procedure.

5. Validation

The validation process is completed within 14 days, and applicants will only have one opportunity to address any questions raised as part of a validation correction request. Failure to adequately address a validation correction request, will lead to invalidation.

The validation timelines have been incorporated into the Route B timetables outlined above, giving applicants sufficient time to complete the validation process between the proposed submission deadline and procedure start date.

If the application initially fails validation or if it is not validated until after the corresponding procedure start date because of an outstanding validation correction request, the procedure start date will be deferred to the following month or until such time as all validation issues are resolved.

6. Post-authorisation IRP applications: variations and renewals

IRP can be used for line extensions, variations (Type 1B, Type II) and renewal applications (including annual renewal of conditional MAs and annual reassessment of exceptional circumstance MAs). Type IA variations can be submitted if they are part of a group with Type IB or Type II variations.

This includes for submissions during the lifecycle of products that have been initially authorised or subsequently varied via direct national, MRDCRP or ECDRP routes. Conversely, where a product has been authorised via IRP, it is acceptable to submit direct national post-authorisation procedures, including variations.

It is recommended that the same RR is used for IRP applications throughout an individual product lifecycle. Marketing authorisation holders (MAHs) may use more than one RR during an individual product lifecycle if this can be justified, for example, on patient benefit grounds. You should highlight changes of RR during the product lifecycle in the post-authorisation procedure cover letter if it differs from the RR used for the initial application.

The relevant published MHRA timetables for national post-authorisation procedures will apply to IRP. The classification of Recognition routes A and B is only applicable for initial IRP MAAs and line extension applications. The eligibility form is not relevant for variations and renewals.

Applicants are reminded of the obligation to notify MHRA as soon as reasonably practicable of any information that might influence the evaluation of the benefits and risks of an authorised product.

IRP is not a substitute for the MAH’s obligations to submit pharmacovigilance data and information to MHRA and to keep the MA up to date with current scientific knowledge. Whilst IRP can be used for safety variations, if there is new data which could impact upon the evaluation of the benefits and risks, particularly where the clinical management of patients may be affected, MHRA must be informed as soon as reasonably practical.

6.1 Variations

Variations submitted via IRP should be classified according to MHRA guidance on variations to MAs. To facilitate lifecycle management of the MA, variations should be submitted as soon as possible after approval by the RR.

MHRA retains the authority to reject a variation application if the supporting evidence provided is considered to be insufficiently robust. MHRA will assess variations which impact on patient safety in the context of the UK clinical situation and we may require assessment through a national route where there are specific UK considerations.

MHRA should be notified in advance of submission if the intended IRP variation will include new information that might impact evaluation of the benefits and risks of a product, clinical management of patients, and/or require proactive communications.  Information should be sent as soon as possible, together with the MAH proposals to: safetyprojects@mhra.gov.uk. MHRA will then confirm if the variation can be submitted via IRP once the RR assessment has concluded or whether a national submission is needed. Failure to inform MHRA of these circumstances may result in a requirement for submission of an urgent national variation.

6.2 Renewals

In order to use IRP for renewals (including the annual renewal of conditional MAs and annual reassessment of exceptional circumstance MAs), applications can be delayed until the reference regulator assessment is completed and the decision available to be included with the IRP submission. The MA will remain valid and the application should be submitted to MHRA as soon as possible, and no later than 60 days following the final assessment and decision being available from the reference regulator.

However, if the reference regulator makes a recommendation at any point during their assessment (whether provisional or final) that the balance of benefits and risks is no longer favourable, there must be no delay in notifying MHRA of this information. As with other lifecycle changes, the original RR is expected to be used for renewal applications.

Applicants are reminded of the obligation to notify MHRA as soon as reasonably practicable of any information that might influence the evaluation of the benefits and risks of an authorised product.

IRP is not a substitute for the MAH’s obligations to submit pharmacovigilance data and information to MHRA and to keep the MA up to date with current scientific knowledge.

7. How to apply

7.1  The applicant

The applicant/MAH must be established in the UK (Great Britain or Northern Ireland) or in the EU/EEA. The applicant for an IRP application should be the same company or belong to the same (legal) group of companies as the MAH of the RR procedure. The applicant can also be a licensee with access to all information needed to fulfil responsibilities and this relationship will need to be demonstrated as part of this application with a written declaration stating that all legal obligations can be met. This is to ensure that the applicant/MAH can fulfil the submission requirements as well as all their legal obligations as holder of an MA, such as the obligations stated in Regulations 74 and 75 of the Human Medicines Regulations 2012 (HMRs).

Provided an applicant can demonstrate and provide written assurance that all the legal obligations can be met at submission, during the assessment process and throughout the life of the MA, it is possible to accept applications from third parties. This requirement applies to initial and lifecycle submissions.

7.2 Scientific advice

It is recommended that scientific advice is requested to ensure the UK requirements can be met. More information on scientific advice can be found here: Medicines: get scientific advice from MHRA - GOV.UK

7.3 Pre-submission meeting

A pre-submission meeting (PSM is not required for IRP applications. However, a PSM can be requested to better understand the procedural requirements for your IRP submission or to discuss a submission for a new active substance or novel therapy. We advise you arrange the meeting to at least 3 months ahead of your intended submission timeline. To request a pre-submission meeting, please complete the IRP pre-submission advice form and submit it to presubmission@mhra.gov.uk.

7.4 Obtaining a product license number

A product licence (PL) number is required before completion of the eligibility form. Companies without a 5-digit company number, should request one from Reference.Data@mhra.gov.uk, to allow registration on the MHRA Submissions Portal. Then request a PL number through MHRA Submissions or by emailing PLNumberAllocation@mhra.gov.uk.

7.5  Eligibility form (new IRP MAAs only)

Suitability for Recognition A or B is determined by means of an online eligibility form to be completed by the applicant at least 8 weeks before the planned date of MAA submission to support MHRA capacity planning. The eligibility checker will provide the applicant with an outcome indicating if they can proceed via Recognition A, Recognition B or if their application will require triage. Where applicable email the eligibility form to Recognition@mhra.gov.uk at least 8 weeks before the intended date of IRP submission.

Eligibility forms requiring triage will need to be sent to Recognition@mhra.gov.uk, where the team will discuss the most appropriate route of submission and respond to the applicant with the outcome in 10 working days.

The following table indicates when and how to submit the eligibility form:

Your product is not a new active substance and the completed form indicates you are suitable for Recognition A or B	Submit the form along with your MAA application.
The completed form indicates that it requires triage by MHRA	Submit the form directly to Recognition@mhra.gov.uk at least 6 weeks before the intended date of MAA submission. On receipt of the eligibility form by email, MHRA will conduct a triage and inform you of the outcome or request further information.
Your product is a new active substance and the completed form indicates it is Recognition A or B	You must notify MHRA of your intention to submit an NAS. To do this, submit the form directly to Recognition@mhra.gov.uk at least 6 weeks before the intended date of MAA submission. You should not expect to be contacted by MHRA prior to submission. Submit the form along with your MAA application.

The form should be included in module 1.2 of the eCTD and the cover letter should indicate which recognition route (A or B) and RR you are using.

7.6 IRP submission

All RR documents submitted in support of an IRP application to MHRA must be in English. A certified translation for any original documents that are not in English together with confirmation in writing that the translation is correct is required.

It is your responsibility to provide the requested documentation. It is not the responsibility of the RR to provide any documentation to MHRA.

See further information on the location of the RR documents in module 1 of the eCTD.

7.6.1 New IRP marketing authorisation applications

Applications should be submitted through the Human Medicines Portal. No other submission route is acceptable for IRP. On submission the system will prompt a response to confirm whether the application is Recognition Route A or Route B or is a recognition variation. Following this there will be a prompt to confirm whether the documentation relates to an original submission

• a validation correction request (VCR)
• a response

The IRP application should be submitted as one electronic Common Technical Document (eCTD) sequence through the MHRA Submissions Portal. The eCTD should be in EU format with a UK-specific module 1. Certain information should be included in the cover letter (see below).

The eCTD submission should be aligned with the consolidated dossier as reviewed and approved by the RR, including the applicant’s full responses to RR questions. It should include approved post-authorisation changes, including variations once approved by the RR. For new IRP MAAs, the submission must include:

• documentation of the RR’s approval decision(s)
• RR’s full unredacted assessment report(s).  All available iterations of the RR’s assessment reports for the initial authorisation and any major post-authorisation procedures (for example, significant variations, renewals) should be provided.
• In cases where an assessment report is not available from the reference regulator, the International Recognition Procedure (IRP) will not be an appropriate route for submission. Applicants are advised to apply via the national procedure in such instances.
• the final product information (or international equivalent) approved by the RR
• a list of differences (other than formatting) between the dossier approved by the RR and that submitted to MHRA

7.6.2 Post authorisation applications

For post-authorisation IRP applications (including variations), the submission must include:

• documentation of the RR’s approval decision
• all iterations of the RR’s assessment reports for the relevant post-authorisation procedure - note that an RR assessment report is not required for Type IB variations, but where available, it should be provided.
• the final product information (or international equivalent) and/or updated risk management plan approved by the RR if applicable.

Where EMA is the RR, a CHMP positive opinion letter is sufficient documentation of approval. Applicants should not submit their IRP applications until they have received the CHMP positive opinion and agreed final product information. For MR-DC recognition, a positive end-of-procedure (EoP) letter is sufficient documentation of approval.

7.6.3 Cover letter

For IRP initial applications to be validated, the cover letter must include the information listed below. See the validation checklist to help ensure all the requirements have been met. This should be submitted with the application as an annex to the cover letter.

For IRP post-authorisation applications, including variations, this information is captured in a validation checklist form that must be completed and submitted as an annex to the cover letter.

The cover letter should  state:

• That the route is International Recognition, who the RR is, and whether it is Recognition A or Recognition B (as determined by the eligibility form which should be included in Module 1.2 with the electronic application form (eAF)).
• For a recognition variation, that the route is International Recognition and who the RR is. If this is different from the authority authorising the initial application this should also be stated each time.  This includes where the initial application was authorised nationally by the MHRA.
• A declaration that all unredacted iterations of the RR assessment reports have been submitted (see reference regulator documents). Assessment reports should be listed.  Where interim assessment reports are not available from the RR this should be declared.
• A confirmation that MAH for the application(s) is the same company or belongs to the same (legal) group of companies as the MAH in the RR procedure. Alternatively, a written declaration that all the legal obligations can be met at submission, during the assessment process and throughout the life of the MA is provided.
• the type of RR approval for initial applications, such as full approval or conditional/provisional/accelerated approval (or international equivalent).
• Any conditions associated with the RR approval, including where the RR has approved a conditional or exceptional use MA (or international equivalent). Details of RR decisions on the fulfilment of any conditions should be included.
• Any proposed conditions for UK approval.

For initial IRP MAAs and extension of indication applications, the wording of the indication approved by the RR should be adapted to take account of UK clinical terminology and practice in accordance with guidance on indications in Volume 2C of the ‘Notice to Applicants’ https://health.ec.europa.eu/document/download/6a043dea-7d0f-4252-947b-cef58f53d37e_en?filename=smpc_guideline_rev2_en.  However it must not differ in scope from that approved by the RR.  All differences between the proposed indication for UK and that approved by the reference regulator should be explained and justified as compliant with the guideline on Summary of product characteristics and consistent with UK practice for the therapeutic area.   

• A justification for the adverse drug reactions (preferred terms and frequencies) listed in section 4.8 of the SmPC, or indicate where in the eCTD module 2 this information is provided.
• If the procedure includes an active substance master file (ASMF), a declaration that the ASMF holder has submitted the applicant’s and restricted parts of the ASMF, including approved variations and the assessment reports on the applicant’s and restricted parts.
• Whether or not there are any differences in the proposed UK RMP compared to the RMP that was approved by the RR (where relevant) and describe any differences in the proposed safety concerns, additional pharmacovigilance activities or additional risk minimisation measures.
• A summary of the UK and global regulatory history of the medicinal product.
• Whether an application for the same product has been approved, withdrawn, refused, or rejected by another RR. Provide reasons for any withdrawal, refusal or rejection.
• Whether a marketing authorisation for the same product has been withdrawn, revoked, suspended or not renewed by another RR. Provide reasons for any withdrawal, revocation, suspension or non-renewal.
• Whether there are any scientific or technical differences between the dossier approved by the RR and that submitted to MHRA. Provide a list of these differences with a justification
• For variations to add a new indication:
  • Confirm whether extended data exclusivity and/or market protection is claimed and if so confirm that section 4c of the application from was updated accordingly.
  • Confirm whether orphan designation for the new indication is applied for and if so confirm that the UK Orphan Drug Designation Application Form has been provided in Module 1.2 of the eCTD.
  • Confirm that all medicinal products granted an Orphan designation in the UK for a condition related to the proposed new indication is captured in section 4a of the application from and that Modules 1.7.1 and 1.7.2 were updated as applicable.
• For submissions that will trigger the paediatric requirements:
  • Confirm that the latest UK paediatric investigation plan, waiver opinion/decision, or class waiver decision has been provided.
  • Confirm that the compliance check outcome document has been provided
  • Confirm whether you are applying for a paediatric “Statement of Compliance” from the MHRA

8. National requirements

The medicinal product must be classified as a medicinal product under the UK Human Medicines Regulations 2012 (as amended). The standard MHRA requirements for a UK marketing authorisation will apply. Further relevant information about national requirements is available in the following subsections.

8.1  Orphan drug designation

IRPs that include an orphan drug designation application will follow the Route B procedure. See further information on orphan drug designation application.

8.2  Paediatric requirements

For submissions that will trigger paediatric requirements, the IRP application dossier must include:

• the latest UK Paediatric Investigation Plan (PIP)/waiver opinion/decision or class waiver decision
• the compliance check outcome documents

If paediatric requirements are triggered in any other jurisdiction, the latest PIP/Paediatric Study Plan (PSP)/waiver opinion/decision or class waiver decision to the MHRA Paediatrics team should be submitted as part of the UK-PIP submission.

Further information is available here: ). https://www.gov.uk/guidance/procedures-for-uk-paediatric-investigation-plan-pips

8.3  Risk management plan (RMP)

The RMP must meet MHRA requirements and follow the EU RMP template. Where appropriate, the format of UK-specific RMP annex + approved EU RMP is also acceptable. For further information on the required format of the RMP, see guidance on pharmacovigilance procedures.

If the RR has not assessed the RMP, the product will be eligible for Recognition B only.

In the case that the RR has approved an RMP, but it is not the same as the RMP proposed for UK or not in the required format, the product will be eligible for Recognition B only.

8.4  Advanced therapy medicinal products (ATMPs)

ATMPs are eligible for Recognition B only. See a definition of ATMPs.

Due to potential differences between guidelines internationally, some IRP applications may require additional checks by MHRA. For example, not all product types are covered by mutual recognition agreements between MHRA and other regulators and some compliance/GMP checks might, therefore, be required by MHRA.

Consequently, applicants are strongly advised to engage with the MHRA at the earliest opportunity through a request for pre-submission advice to discuss the submission and any potential difficulties that may be encountered.

See: Pre-submission Advice & Support - GOV.UK (www.gov.uk) how for to contact us.

Furthermore, some product classes have different definitions internationally which means that MHRA might have to check that the application in question does indeed fall within MHRA’s remit and within MHRA’s classification for such products.

8.5 Environmental risk assessment (ERA)

The ERA needs to have been assessed by the reference regulator for the product to be eligible for Recognition A. If the ERA has not yet been assessed by an RR, the product will be eligible for Recognition B only. In the case that the RR has approved an ERA, but it is not the same as the ERA proposed for UK or not in the required format, the product will be eligible for Recognition B only.

8.6 Good manufacturing practice (GMP)

Confirmation is required that all manufacturing sites have a current GMP certificate that meets MHRA requirements.

If a new site is added specifically for MHRA, the application is eligible for Recognition B only.

If the site in question has no relevant inspection history, the timelines for the recognition process may be extended until an inspection has been successfully completed.

Where available, inspection information from Mutual Recognition Agreement (MRA) partners and Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) participating authorities should be submitted to support verification of the GMP status of manufacturing sites based in third countries. This information will be utilised in accordance with the principles of PIC/S Inspection Reliance.

GMP Inspection information required, as a minimum:

• Information relating to the latest inspection by the hosting NCA. For example:
  • dates on site, inspection scope and outcome, inspection report, company response/corrective and preventative action (CAPA) plan, and planned re-inspection date (if known).
• Post inspection information provided by the hosting NCA on justified request
• Information relating to inspections by other regulatory authorities in a defined time period (e.g. previous 2 years or since the previous inspection by the regulatory authority performing the assessment). For example:
  • name of regulatory authority, dates on site, inspection scope and outcome, and planned re-inspection date (if known/applicable). Inspection reports and company responses could also be requested, as appropriate.
• Site master file (typically this will be in the EU-PIC/S format).
• Information to aid in an assessment of risk. For example:
  • changes since the last inspection by the hosting NCA to key site personnel or personnel numbers, company ownership, and processes and products (e.g. changes in the types or numbers of products manufactured/handled, previously outsourced activities that have been brought back in house).

8.7  Nitrosamine risk assessment

Before the recognition procedure for a new product can be approved, you must provide a nitrosamine risk assessment and outcome in line with MHRA guidance. For more information see Medicines: Marketing Authorisation Holders’ submission of Nitrosamine risk evaluation, risk assessment and confirmatory testing - GOV.UK.

8.8  Generic, hybrid and biosimilar applications

Reference Medicinal Product

Following implementation of the Windsor Framework on 1 January 2025, applications relying on a reference medicinal product must cite a UK reference product.   Published guidance on reference medicinal products can be found here:  Reference Medicinal Products (RMPs) - GOV.UK (www.gov.uk).

Applicants must ensure that there is no infringement of reference product data or market exclusivity periods (DME).

For generic and biosimilar applications (made under Regulations 51B or 53B respectively) the proposed indications and posology must be in line with the UK reference product.

• If the application is for indications approved by the RR but which are different from or more extensive than those approved for the UK reference medicinal product the application must be submitted as a hybrid application under Regulation 52B of the Human Medicines Regulations 2012 (as amended) and the reference regulator’s assessment of those indications must be provided.

• If the posology approved by the RR is different from that approved for the UK reference medicinal product the application must be submitted as a hybrid application under Regulation 52B of the Human Medicines Regulations 2012 (as amended). and the reference regulator’s assessment of those indications must be provided

• If the indications approved by the RR are more restrictive than those approved for the UK reference medicinal product the application may still be submitted as a generic or hybrid application under Regulation 51B of the Human Medicines Regulations 2012 (as amended) but the difference in indications must be highlighted in the cover letter.

Comparator Product for bioequivalence or therapeutic equivalence testing

Bioequivalence between generic and UK reference products should be demonstrated in accordance with requirements applicable  in the UK: Investigation of bioequivalence - scientific guideline. This guidance provides advice on the study design and on acceptance criteria. 

From 1 January 2025, in the case of generic or hybrid medicines, if the comparator product used in the bioequivalence or therapeutic equivalence study was not sourced from the UK/EU/EEA market, refer to advice on how to demonstrate that the comparator product used is representative of the UK reference medicinal product.

For biosimilars, see MHRA guidance for biosimilars.

8.9  Active substance master file (ASMF)

If Module 3 does not include full information on the active substance or a Ph. Eur. Certificate of Suitability, then an ASMF should be submitted. See RR assessment documents section below.

If an ASMF has been submitted to the reference regulator for the application in question, the ASMF holder must submit an identical copy of the complete ASMF (applicant’s and restricted parts) to MHRA.

Modules 2.3 and 3 must be submitted in consolidated form together with relevant sections of Module 1 according to MHRA requirements that includes the letter of access, the assessment report from the restricted part, the list of questions and the response of the ASMF holder to the questions on the restricted part.

If the ASMF has been subsequently modified - after first authorisation and before submission to MHRA - the approved variations, with the corresponding assessment reports, must be submitted separately in parallel and noted in the cover letter together with a comparison showing the changes (old/new).

The version number of the applicant’s and restricted parts of the ASMF as approved by the reference regulator should be clearly stated in the cover letter, along with a confirmation that these versions have been submitted to MHRA. Please reference the submission CESP/Portal ID number.

8.10 Plasma products

Fractionated plasma products are eligible for Recognition B only.

Plasma products must meet all relevant UK requirements in particular with regard to viral safety and donor eligibility and they must comply with relevant European Pharmacopoeia (Ph Eur) monographs. Guidance has been published here: https://www.gov.uk/guidance/licensing-plasma-master-files-and-vaccine-antigen-master-files.

8.11 Compendial requirements

References to compendia in Module 3 will need to be to either the British Pharmacopoeia (BP) or Ph. Eur., unless otherwise justified. 

9. Fees

Fees charged by MHRA can be found here: MHRA fees.

Use the Fees calculator to work out the correct fee.

10. Reference regulator documents for initial IRP MAAs

The lists below show the documents that comprise a complete assessment for each RR.

The full set of documents is expected for new active substances. In other cases all available assessment reports must be provided even if they are not marked as mandatory below.  

Items marked with ** are mandatory requirements in all cases. Other documentation is required where it has been issued or published by the Reference Regulator.

Reference regulator: European Medicines Agency (EMA)

For applications submitted through the EMA’s centralised procedure, a CHMP positive opinion is an RR approval for the purposes of submitting an IRP application; it is not necessary to wait for the European Commission notification of grant.

Documentation:

• Interim centralised procedure assessment reports
• final CHMP assessment report**
• final product information**
• summaries of meetings with the EMA and/or rapporteurs (including scientific or pre-submission advice, where relevant)
• Orphan maintenance assessment report (where relevant)
• CHMP summary of opinion**
• post marketing review(s)

Reference regulator: EU member states MR/DC requirements

The MRDC positive end-of-procedure outcome is an RR approval for the purposes of submitting an IRP application. It is not necessary to wait for the grant of national MAs following the end of procedure. The end of procedure date of the latest MRP Repeat-Use Procedure can be used for the purpose of establishing the 2 or 10 year eligibility periods.

Documentation:

• all assessment reports including overview and full versions of the quality, non-clinical, clinical and risk management plan**
• questions from the regulator to the applicant/ MAH (and responses)**
• summaries of meetings with reference member state (RMS) and concerned member states (CMS) including scientific or pre-submission advice, where relevant
• RMS positive end of procedure letter**
• final assessment report**
• final common product information**

Reference regulator: EU member states national requirements

Documentation:

• all assessment reports including overview and full versions of the quality, non-clinical, clinical and risk management plan**
• questions from the regulator to the applicant/MAH (and responses)**
• summaries of meetings with the member state competent authority (including scientific or pre-submission advice, where relevant)
• final product information**
• approval letter/documentation**
• post marketing reviews

Reference regulator: Pharmaceutical and Medical Devices Agency (PMDA), Japan

Documentation:

• discussion documents, questions from PMDA and answers provided, and finalised minutes from scientific consultation meetings (if applicable)**
• outcome of orphan designation, priority or SAKIGAKE determination (if relevant)
• copies of questions and answers exchanged between sponsor and PMDA
• unredacted English translated review reports and outcome **
• report on the deliberation results**
• final product information**
• approval Letter/documentation**
• post-marketing review(s)

Reference regulator: Health Canada

Documentation:

• clinical review: pharmaceutical safety and efficacy assessment report (PSEAR)** (except for generic applications)
• quality: quality evaluation summary (QES) and manager’s memo**
• non-clinical report** (except for generic applications)
• bioequivalence: comprehensive summary – bioequivalence (CS-BE) and manager’s memo (if applicable)**
• biostatistics: biostatistics consult report (if applicable)
• questions from the regulator to the applicant/MAH (and responses)**
• summaries of meetings with Health Canada (including scientific or pre-submission advice, where relevant)
• final product information**
• approval letter/documentation**

Reference regulator: Health Sciences Authority (HSA), Singapore

Documentation:

• questions from the regulator to the applicant/MAH (and answers)**
• HSA assessment of responses to questions**
• final quality, non-clinical and clinical reports and summaries, where applicable**
• (risk management plan assessment where applicable)**
• summaries of meetings with HSA (including scientific or pre-submission advice, where relevant)
• approval letter/documentation**
• final product information**
• post marketing reviews

Reference regulator: Therapeutic Goods Administration (TGA), Australia

Documentation:

• all assessment reports including quality, non-clinical and clinical (where applicable) and risk management plan.
• questions from the regulator to the applicant/MAH (and responses)**
• summaries of other meetings with the TGA (including scientific or pre-submission advice, where relevant)
• approval letter/documentation**
• final product information**
• post marketing review(s)

Reference regulator: SwissMedic, Switzerland

Documentation:

• all assessment reports including quality, non-clinical and clinical(where applicable) and risk management plan
• questions from the regulator to the applicant/MAH (and answers)**
• summaries of meetings with SwissMedic (including scientific and pre-submission advice, where relevant)
• approval letter/documentation**
• final product information**
• post marketing reviews

Reference regulator: United States Food and Drug Administration (US FDA)

Documentation :

• medical review(s)**
• chemistry review(s)**
• pharmacology review(s) (where applicable)
• statistical review(s) (where applicable)
• non-clinical review(s) (where applicable)
• clinical pharmacology biopharmaceutics review(s)(where applicable)
• risk assessment and risk mitigation review(s)**
• administrative document(s) and correspondence
• questions from the regulator to the applicant/MAH (and answers)**
• cross discipline team leader review (if issued)**
• office director memo, where relevant (if issued)**
• summaries of meetings with the US FDA (including scientific or pre-submission advice, where relevant)
• summary review
• final FDA label**
• approval documentation/letter**
• post marketing reviews

11. Contact

Please find below a list of relevant contact points to discuss your IRP application:

• If your enquiry relates to the Eligibility Checker indicating that triage is required by the MHRA, email Recognition Recognition@mhra.gov.uk

• If your enquiry relates to your product being a New Active Substance (NAS), the eligibility form should be emailed to Recognition Recognition@mhra.gov.uk

• If you do not have a 5-digit company number, to allow registration on the MHRA Submissions Portal, you should request it from Reference.Data@mhra.gov.uk

• A PL number can be obtained through MHRA Submissions or by emailing PLNumberAllocation@mhra.gov.uk.

• If you would like to request a pre-submission meeting to discuss your application via the International Recognition Procedure, then please complete the IRP pre-submission advice form and email it to presubmission@mhra.gov.uk.

• For further information on the International Recognition Procedure, complete the IRP contact form and email it to ris.na@mhra.gov.uk