On 7 October, the MHRA issued a consultation document setting out its proposed guidance on the licensing and regulation of biosimilar products in the UK.
Prior to the UK leaving the EU, the licensing and regulation of biological medicinal products was the preserve of the EMA. After the expiry of the transition period on 31 December 2020, the MHRA will assume this role and the consultation document setting out the approach it intends to take is therefore an important document.
Encouragingly and sensibly, the MHRA is not looking to rewrite the approach taken by the EMA. At the outset of the guidance document, applicants for a biosimilar licence are encouraged to consult the existing guidance on biosimilars issued by the Committee for Medicinal Products for Human Use (CHMP), signalling straight away that it is a 'steady as she goes' approach. However, while not seeking to reinvent the wheel, the MHRA guidelines do indicate that there are some revisions that will be introduced to take account of the wealth of experience that has been accumulated in the regulation of biosimilars since 2006. Nonetheless the similarity in the approach is notable, and will be welcomed to ensure the future supply and sale of UK biosimilar products into the EU.
Biosimilarity Principles
The biosimilarity principles expressed in the guidance are as would be expected. In the first instance there would be a reference product (RP) already on the market in the UK or the EU which must have been approved on the basis of a complete dossier (a RP from outside of the UK/EU will requires further bridging data).
Thereafter, and as is the case with biological references, the biosimilar must be "highly similar" to the RP in terms of the biological, physiochemical and potency characteristics. The active substance must be the same. The posology (or dosage) and route of administration must be identical to those of the RP. Any deviation will almost certainly require justification and further data.
The Application for a Biosimilar Product
There are some points worth noting about what an applicant is required to submit to the MHRA to show compliance with the biosimilarity principles. While there is considerable alignment with the CHMP guidance there are some differences. These are:
- The RP – these must be clearly identified and include comprehensive information including the name, source, strength, formulation and the batch number.
- Biosimilarily comparability – naturally, a comprehensive analysis of all batches of the biosimilar and the RP is required, taking into account the number of batches of each one and ideally this will include an analysis of biological activity and in-vitro fundamental activity. Any differences detected will need to be justified and must not impact on clinical efficacy.
- It is worth noting that while a confirmatory pharmacokinetics (PK) trial is required, the application will NOT be required to include:
- in most cases, a confirmatory efficacy trial if the application is supported by appropriate comparable analytical and functional data;
- any animal studies.
- There will also be no requirement for repeat demonstrations of biosimilarity following the grant of the licence for the biosimilar product.
- Post grant of the licence there will of course need to be a full Risk Management Plan to reflect the risk associated with the RP, including any additional pharmacovigilance activated.
Once a licence is granted for the biosimilar product it is considered interchangeable with the RP, although the decision on switching will continue to rest with the prescriber in consultation with the patient.
As we say, the approach taken by the guidance document is encouraging, maintaining consistency with CHMP principles while at the same time refining the approach in the light of past experience.