The market authorisation of biosimilars has to date been held up in Europe (and elsewhere) by the absence of a regulatory pathway for their approval. The recent transposition into French law of the European community code on medicinal products for human use (European Directive 2004/27/EC) marks an important step on the road to establishing common regulatory procedures.
The biotech industry has welcomed the adoption of the new medicines law, which confirms the European Union’s legal definition of biosimilars, which in the French law are referred to as ‘biologically similar drugs’. It recognises that biosimilars are different from chemical generic drugs, owing to differences based on the variability of active biotechnological substances and manufacturing processes. The law also states that the granting of market authorisation for such products will require preclinical and clinical data.
Attention has also focused on the substitutability of original biotech products and biosimilars: owing to the fact that the two cannot be considered to be identical, automatic substitution by pharmacists should not be allowed without the consent of a physician.
|
Adding Value: Biosimilars Biosimilars are the biotechnology equivalent of chemical generics – except they are only therapeutically similar to the original product, rather than chemically identical. This puts them in an unusual regulatory position because biopharmaceuticals are defined by their production process, and it is impossible to replicate exactly the biological process for large molecules. As a result, it is difficult to prove essential similarity or equivalence – vital to demonstrate safety and efficacy – without investing in clinical trials and a completely new filing. These are costs not borne by chemical generics, which benefit from an abbreviated process that draws on the original product’s filing. |
Biotech industry reaction
Carlo Incerti, President of European Biopharmaceutical Enterprises (EBE), was very positive about the new legislation: “France is to be congratulated on striking that delicate balance between regulating biosimilars and showing necessary precaution in the protection of patient safety… In order for physicians to be able to monitor their patients for any unexpected or adverse immune reactions, it is essential that they retain control over the treatment and therefore important that automatic substitution at the level of the pharmacy is not permitted for biotech, including biosimilar medicines. France really serves as an example for other countries.”
Speaking to IMS, EBE’s Executive Manager, Emmanuel Chantelot, emphasised the initiative being taken by the French authorities in this respect. “The focus on biosimilars and the clear reference to the fact that automatic substitution should not be allowed is significant for France and for the rest of Europe. France is the first member state to make this clear through a law and as a result has created a precedent for other countries looking at this. There has been no clear view expressed on this issue by European institutions: in this respect, it can be seen that this has been deferred to member states. In this case, one important state, France, has adopted legislation and thus set an important precedent.”
Andrea Rappagliosi, Chairman of the Healthcare Council of EuropaBio, the EU association for bioindustries, reinforced this view: “The development is important because it paves the way for customisation at the national level: so doctors, pharmacists and patients are aware of what is happening with these products. The legislation brings clarity in France, making it clear to the patient, pharmacist and physician that a biosimilar is not the same as a generic,” he told IMS.
“We really welcome the development in France,” continued Rappagliosi, “as the authorities have not traded off under some potential economic benefit. Internationally, what is important is that it is seen that a member state can take the lead.” Spain may be next in line: “The authorities are working on implementation that may be very similar to the approach taken in France. However, this of course needs to be seen in the context of an environment in which countries have their own healthcare systems,” cautioned Rappagliosi.
For Thomas Bols, Chair of EBE’s task force on biosimilars, the French development draws attention to the special status of biotech, as well as biosimilar products, when compared with chemical drugs. “In France, it is clear that biosimilar products are seen to be not the same as generics. Marketers of biosimilar products will recognise that they cannot sell them like generics and will have to sell [and] support them like innovator products. This will require additional investments, which will have an impact on the economics of biosimilars.
“An issue here, and for other countries looking at what has happened in France, is about what is appropriate for biotech products in general, not just biosimilars. However, the introduction of biosimilars has initiated the debate,” Bols told IMS.
Alternative perspective
The European Generic Medicines Association (EGA) has a somewhat different take on the French development. According to EGA’s Senior Director of Scientific & Regulatory Affairs, Suzette Kox: “The new legislation does allow interchangeability of biological products, which is practised throughout Europe. EGA distinguishes interchangeability, which is a clinical decision at formulary committee or clinician level and substitution, which takes place at the retail pharmacy level and is a purely national decision.”
Kox continued: “It may be worth highlighting that the first generations of biosimilar medicines are all biotechnology-derived medicines (human growth hormone, insulin, erythropoietin, interferons, G-CSF and so on). They are not or cannot be approved by the French agency [Agence Française de Sécurité Sanitaire des Produits de Santé, AFSSAPS] but by the European Commission, which bases its decision on the CHMP [the Committee for Medicinal Products for Human Use] positive scientific opinion, which is a European-wide opinion. Furthermore, a large number of these existing or expected biosimilars are hospital-dispensed products and are consequently not covered by the substitution law at retail pharmacy level and therefore not affected by the new provision in France.”
The Chair of EGA’s Biosimilars and Biotechnology Committee, Tim Oldham, told IMS: “We would like to urge the French authorities not to consider this the ‘end game’, but to engage in scientific discussions to determine the circumstances under which biosimilar products might become automatically substitutable. Inevitable variability exists between batches of the same originator biological product as well as between the ‘old’ and ‘new’ originator product after a manufacturing change such as a change in source material, manufacturing process or cell line – or even a change in manufacturing site. Automatic interchangeability occurs in practice today between these non-identical versions of the same originator product where the efficacy and safety characteristics are not significantly different – the same criteria applied to the approval of biosimilar medicines.”
Extracted from Pharma Pricing & Reimbursement, published monthly by IMS Health. For further information, please contact Nicky Richards, or call +44 1223 273200.