Reference Medicinal Products (RMPs) in the UK Regulatory Framework

1. What is a Reference Medicinal Product?

A Reference Medicinal Product (RMP) is an existing authorised medicinal product that provides the clinical and regulatory data basis against which bioequivalence and therapeutic equivalence are demonstrated in abridged marketing authorisation applications (for example, generics, biosimilars or hybrid medicines). RMPs underpin the comparison work needed to support a new applicant’s submission to the Medicines and Healthcare products Regulatory Agency (MHRA).
Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)

2. Legal Basis and Current Definition

The criteria for RMPs in the UK are set out under Regulation 48(2) of the Human Medicines Regulations 2012 (as amended). For applications intended to result in a UK-wide marketing authorisation (MAA), the RMP must be a product that has been authorised for at least 8 years in the UK or meet similar conditions under UK law.
Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)

Since 1 January 2025, following implementation of the Windsor Framework, applicants must cite a UK-authorised product as the RMP in UK-wide generic, hybrid or biosimilar applications. Products authorised only under previous EU frameworks or without valid UK authorisation cannot be cited in new UK-wide applications.
Source: UK-wide licensing for human medicines: supplementary guidance

3. Use of RMPs in Abridged Applications

In an abridged application for a new generic or similar product, the applicant must demonstrate that the proposed product is bioequivalent to the RMP (bioavailability, therapeutic equivalence, quality). This typically includes comparative analytical and clinical data referencing the RMP.
Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)

RMPs also support the interpretation of data from bioequivalence (BE), pharmacokinetic (PK) and therapeutic equivalence (TE) studies that form part of the regulatory dossier. These comparator products must be representative of the UK RMP, and where sourced outside the UK, applicants may need to justify representativeness with adequate scientific evidence.
Source: UK-wide licensing for human medicines: supplementary guidance

4. Changes Under the Windsor Framework

Prior to 1 January 2025, some UK marketing authorisation applications could refer to products with EU marketing authorisations as RMPs if they met specific criteria. However, with the Windsor Framework’s implementation, only products authorised in the UK for the requisite period can serve as RMPs in UK-wide applications.
Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)

This change aligns RMP selection with the UK’s national regulatory regime, strengthening the use of UK-based data and authorisations for the assessment of abridged applications.
Source: UK-wide licensing for human medicines: supplementary guidance

5. Non-UK and Northern Ireland Specific Considerations

For applications intended only for Northern Ireland, EU requirements may continue to apply for RMPs under the Northern Ireland Protocol. In such cases, EU-authorised reference products may still be relevant if they comply with the applicable EU rules.
Source: UK-wide licensing for human medicines: supplementary guidance

6. Practical Implications for Applicants

Applicants preparing generic, biosimilar or hybrid applications should:

• Identify a valid UK-authorised RMP that meets the regulatory criteria.
• Provide robust comparative data demonstrating equivalence to the RMP.
• Ensure that bioequivalence and therapeutic equivalence studies utilise appropriate comparator products representative of the UK RMP.
  Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)

Conclusion

Reference Medicinal Products remain foundational in the UK regulatory framework for abridged marketing authorisations. The emphasis on UK-authorised RMPs post-2025 underscores the MHRA’s focus on national data and authorisation histories in assessing generics, biosimilars and hybrid product applications.
Source: Reference medicinal products (RMPs) (gov.uk) (gov.uk)