In the event of a no-deal Brexit, reference medicinal products (RMP) for new generic medicines or abridged marketing authorisation applications will be required to comply with the Human Medicines Regulations 2012, as amended by the Human Medicines (Amendment etc.) (EU Exit) Regulations 2019 (HMRs). Comparator products (CP) used in these applications will need to be representative of the RMP.
The reason for determining pharmaceutical equivalence against the CP is to demonstrate that the safety and efficacy of the proposed medicinal product is equivalent to that of the UK RMP, for which safety and efficacy has previously been confirmed. The guidance offers an explanation of the criteria to be considered when choosing a CP for bio-equivalence (BE), pharmacokinetic (PK) and therapeutic equivalence (TE) studies.
In the event of a no-deal Brexit, the CP should be sourced from the United Kingdom (UK). However, if this is not possible then the applicant will need to provide evidence that their non-UK CP is representative of the RMP. The licensing authority will need to be satisfied that the difference between the non-UK CP and UK RMP is not therapeutically significant.
The non-UK CP should be authorised in a country with similar regulatory standards to the UK, such as EU countries, USA, Canada, Australia or Japan. The non-UK CP is not required to be identical to the RMP. Minor differences such as tablet coating colour, score-lines, flavour and container closures will be accepted, provided that bridging data supporting their relevance to the UK RMP is scientifically justified, as this may affect safety and efficacy. The guidance details the information which will need to be included in Module 1.5.2 of the Common Technical Dossier (CTD) regarding bridging data for both the RMP and non-UK CP.
If the non-UK CP is identical to the UK RMP, written confirmation from the Marketing Authorisation Holder (MAH) of the non-UK CP will need to be submitted, including the identicality of:
- the route of synthesis of the drug substance(s)
- the drug substance specifications
- the finished product quantitative composition
- the manufacturing process including in-process controls
- the finished product specifications
- the stability data
The MHRA states that “if representativeness between the non-UK CP and the RMP cannot be demonstrated, BE and TE studies should be performed against the RMP in the UK”. A final decision on the safety, efficacy and quality of the medicinal product will only be made during assessment of the application. To access the full guidance, click here.