Comparator products in the post-Brexit world

Comparator products for use in bioequivalence and therapeutic equivalence studies for Great Britain are covered in the UK government guidance Comparator products in Bioequivalence/Therapeutic Equivalence studies from 1 January 2021 (1 September 2020). The scope of the guidance only covers applications relating to generic medicinal products (regulation 51 of the Human Medicines Regulations 2012) and applications relating to certain medicinal products that do not qualify as generics (regulation 52 of the Human Medicines Regulations 2012), but the guidance makes clear that the principles may also be applicable for other forms of applications (Regulation 54, 55 and 65C of the Human Medicines Regulations 2012). Comparator products for applications in Northern Ireland continue to be covered by the EU requirements.

Generally, the comparator product used in bioequivalence, pharmacokinetic or therapeutic equivalence studies should be sourced from Great Britain. A non-GB comparator product should be authorised in and sourced from a country that has similar scientific and regulatory standards to the UK. Examples of such countries are the EU/EEA, Switzerland, USA, Canada, Australia and Japan. The non-GB sourced comparator product would normally be expected to be part of the same global marketing authorisation as the reference medicinal product, or marketed in the non-GB country through a licensing arrangement with the entity that currently markets the product in Great Britain.

Where a non-GB sourced comparator product is used, an eligible reference medicinal product must still be referred to in the application for a new medicinal product. If the non-GB sourced comparator product can be shown to be identical to the eligible reference medicinal product, then no further data is required. Identicality can be shown by written confirmation from the MA holder of the comparator product. Otherwise, it must be demonstrated that the non-GB sourced comparator product is representative of the eligible reference medicinal product. The applicant should provide adequate comparative, experimental data or information to justify the relevance of the comparator product and establish an acceptable bridge to the reference medicinal product. This bridging data must always include data from analytical studies that compare the reference medicinal product, the non-GB sourced comparator product and the proposed medicinal product. Comparative data from at least 3 batches of each of the non-GB sourced comparator product and the eligible reference medicinal product are usually expected.

If representativeness between the non-GB sourced comparator product and the eligible reference medicinal product cannot be demonstrated, then bioequivalence and therapeutic equivalence studies will need to be performed in Great Britain between the new medicinal product and the reference medicinal product.

The exact type of data that are required are assessed on a case-by-case basis. If the application relates to a product of a certain type (including products that do not exhibit immediate release of the drug substance, products not for oral administration, products with a narrow therapeutic range or safety margin, products with a risk of serious undesired effects), it is recommended that the applicant contact the MHRA for advice.

Applications for which there is no eligible reference medicinal product are advised to contact the MHRA for advice. Applicants for more complex products are also encouraged to contact the MHRA for advice.

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