The European Medicines Agency has issued a draft guidelines for public consultation on biosimilar medicinal products that replaces the previous guideline that came into effect in October 2005.
IHS Global Insight perspective | |
Significance | The European Medicines Agency has published a revised version of the guidelines on biosimilar medicinal products that entered into force on October 2005. |
Implications | The draft guidelines are updates that encompass substantial changes, for example medicines sourced from outside the European Economic Area which are now accepted as reference products. |
Outlook | The public consultation on these draft guidelines will be open until 31 October. |
The European Medicines Agency (EMA) has published draft guidelines on biosimilar medicinal products, seeking to update the existing guidelines. The draft guideline, which would replace the previous guideline approved in October 2005, outlines the general principles to be applied for similar biological medicinal products, or biosimilars. The revised guideline focuses on the application of the biosimilar approach, the choice of the reference product and the principles of establishing biosimilarity. The draft guideline is open for public consultation until 31 October. The full draft guideline is available here.
The "biosimilar approach"
The draft guideline provides a clear definition of biosimilar products that are indentified as: "A biological medicinal product that contains a version of the active substance of an already authorised original biological medicinal product (reference medicinal product). A biosimilar demonstrates similarity to the reference medicinal product in terms of quality characteristics, biological activity, safety and efficacy based on a comprehensive comparability exercise."
As in the previous version, the guideline highlights that the generic approach applied to chemically-derived medicinal products is not applicable to biological or biotechnology-derived products. Therefore, a "biosimilar approach" must be applied for these products.
In addition, the guideline stresses that the biosimilar comparability is easier to be exercised with highly purified products. Conversely, with regard to other products, for example biological substances arising from extraction from biological sources or those for which little clinical and regulatory experience has been gained, biosimilar comparability exercises may be more complex.
Furthermore, changes aimed at improving efficacy of the candidate biosimilar product vis-à-vis the reference medicinal product are not considered compatible with the biosimilarity approach.
Identification of reference product
The draft guideline encompasses a substantial change that was introduced in September 2009 further to the European Commission decision to accept batches of reference medicines sourced from countries outside the European Economic Area (EEA). The decision was driven by the intention to enhance the development of biosimilars in Europe.
The guideline maintain as a preferential mechanism the use of a medicinal product authorised within the EEA area as basis for the biosimilar product approval. However, in order to facilitate the diffusion of biosimilars products and to avoid repetitions in clinical trials, "it may be possible for an applicant to compare the biosimilar in certain clinical studies and in vivo non-clinical studies (where needed) with a non-EEA authorised comparator (i.e. a non-EEA authorised version of the reference medicinal product) which will need to be authorised by a regulatory authority with similar scientific and regulatory standards as EMA (i.e. ICH countries). In addition, it will be the applicant's responsibility to establish that the comparator authorised outside the EEA is representative of the reference product authorised in the EEA". In addition, when studies of the development programme are exclusively carried out with a non-EEA authorised comparator, it is the responsibility of the applicant to provide data and information that is able to be bridged to the EEA-authorised reference products. However, the comparator selected must be a product approved by a regulatory authority that shares regulatory and scientific standards similar to the ones applies by the EMA.
Biosimilar development programme
A biosimilar development programme is designed to evaluate the similarity between the biosimilar and the reference product. The biosimilar product is required to be highly similar to the reference medicinal product both in its physicochemical and biological characteristics. Therefore, deviations from this criterion have to be accurately justified in terms of safety and efficacy. However, although improvements in terms of safety need to be thoroughly justified, they may not compromise biosimilarity approval.
Outlook and implications
The revision of the guidelines issued in 2005 is an essential step in order to enhance the market penetration of biosimilar products in Europe, while also clarifying the principles and requirements that constitute the basis for the approval of biosimilar products in the European Union. Since the approval of the first version of the guidelines, 14 biosimilars have been approved and five applications are under consideration in the EU. As highlighted above, substantial changes were already introduced over the years in order to facilitate the approval process.
One of the essential changes reflected in the revised version is the possibility to use products approved outside the EEA as a reference product. Other countries, for example Canada, that have introduced biosimilar guidelines after the EU guideline was issued in 2005, have left open the possibility of using a medicinal product authorised by other countries as ra eference product (see Canada: 08 April 2008: Health Canada Publishes Draft Biosimilars Approval Guidelines). Allowing the use of a reference drug which is not authorised in Europe makes the current draft guidelines more flexible than the biosimilars development guidelines currently in effect.
In addition, it is worth noting that the guideline explicitly excludes the improvement of the efficacy of the candidate biosimilar products as efficacy improvement is not recognised within the biosimilarity approach. IHS Global Insight's interpretation of this clause is that it is advisable for companies which succeed in improving the efficacy of a biosimilar product they are developing vis-a-vis the efficacy of the originator to seek approval under the originator biologic route instead of using the biosimilars route. In addition, following the originator route, if the product is granted marketing authorisation approval by the European Commission, it may also have an easier route to reimbursement and a favourable price in EU member states which value "improvement" over existing therapies.
The final version of the guideline may differ from the draft depending on the comments received from stakeholders during the consultation period.