Biosimilars & Biologics
Key legal info on biosimilars & biologics in Swiss Pharma. Prepared in association with Wenger Plattner, a leading law firm in Switzerland, this is an extract from The Pharma Legal Handbook: Switzerland, available to purchase here for GBP 99.
1. Are biosimilar medicines considered the same as generic medicines in your country?
No, compared to generics with chemically synthesized active ingredients, the production of biosimilars is much more complex, and further requirements must be met for their approval.
2. Are all biologic medicines, including biosimilar medicines, patentable in your country?
Under current law, no initial notification protection (patent) is granted for biosimilars. Upon receipt of an application for authorisation of a biosimilar, Swissmedic examines a possibly ongoing first filing protection for the reference product according to Article 12 Remedies Act (HMG). If the initial notification protection has not yet expired at the time of receipt of the application, or if there is no corresponding consent from the marketing authorisation holder of the reference product, Swissmedic will not proceed with the biosimilar application. Indications, new routes of administration, new dosage forms or new dosages for reference products that are still protected may not be applied for in the case of a biosimilar. As a matter of practice, Swissmedic does not act on such applications.
3. Is there a specific regulatory framework for the marketing authorization of biosimilar medicines in your country? If yes, what is the regulatory framework for the authorization of biosimilar medicines?
For the approval of a biosimilar, manufacturers must prove that the biosimilar is sufficiently similar to a “reference preparation in terms of structure, pharmaceutical quality, biological activity, efficacy, safety and immunogenicity to exclude relevant clinical differences with sufficient certainty”. These characteristics of a biosimilar must be documented by its manufacturer through physicochemical and biological characterization of the biosimilar, as well as through comprehensive preclinical and clinical studies (“comprehensive comparability exercise”).
If the approval criteria are met, the manufacturer receives approval for the drug. The sales method and the professional and patient information are determined and approved by Swissmedic.
4. What kind of data package is needed to obtain approval for a biosimilar drug? Is this any different to the requirements for the original Biologics drug?
The data requirements for approval differ between reference products and biosimilars, as the approval procedure for biosimilars does not aim to provide renewed evidence of the efficacy and safety of the active substance. Rather, the process aims to demonstrate biosimilarity to the reference product.
For this purpose, comprehensive analytical, non-clinical and clinical comparability studies to the reference product and solid data on pharmaceutical quality are required. These comparability studies represent the cornerstone of biosimilar development and approval. The aim of these comparative studies is to exclude potential product-related differences that could affect pharmacokinetics and dynamics, efficacy or safety.
5. What are the requirements for the choice of the reference comparator product?
In principle, manufacturers are free to decide for which indications and dosage recommendations of the reference product an authorization of the biosimilar is applied for. If the comparability of the reference product and biosimilar in terms of efficacy and safety has been documented for at least one sensitive indication and dosage, the comparability of the active substances can also be “extrapolated” to other indications. In this context, in the case of complex mechanisms of action and multiple target receptors, additional comparative analyses may be necessary in isolated cases, particularly for immunogenicity. Which indications or dosage recommendations are permissible for the biosimilar by extrapolation from the reference product is decided by Swissmedic on a case-by-case basis.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
No, there has never been a corresponding approved reference product in Switzerland, thus, no biosimilar approval is possible in this respect.
7. How are the prices of biosimilar medicines regulated? Is this any different from the requirements for the original Biologics drug?
In contrast to original products, whose cost-effectiveness is determined based on the APV and TQV, the cost-effectiveness test for biosimilars is based on a price gap rule compared to the reference product.
The FAP of the biosimilar is determined upon new inclusion in the SL in such a way that a price gap of at least 25 percent is maintained compared to the reference product. Only then are biosimilars considered economical. Every three years, the Federal Office of Public Health (FOPH) reviews the price of the reference product. In this context, the price of the biosimilar is also adjusted. The biosimilar is economic if the price difference to the reference product is at least 10%.
Moreover, the price of a biosimilar is at least 25% below the price of the reference product at market launch.
8. What is the reimbursement policy for biosimilar medicine? Is this any different from the requirements for the original Biologic drug?
An obligation to reimburse medicinal products by the compulsory health care insurance (OKP) exists only for medicinal products and indications that are on the SL of the Confederation. The Federal Office of Public Health (FOPH) decides on the inclusion of the drug in the SL (the SL is a conclusive positive list that is binding for insurers) and its reimbursed definitive price, in the case of new innovative drugs with the inclusion of the recommendation of the Federal Drug Commission. Medicinal products and indications that are not on the SL can be reimbursed in individual cases according to Art. 71a-c of the Ordinance on Health Insurance (KVV) if “the use of the medicinal product is expected to have a major therapeutic benefit against a disease that may be fatal for the insured person or result in severe and chronic health impairments, and no other effective and approved treatment method is available due to a lack of therapeutic alternatives”. In addition, reimbursement is possible in individual cases if the use of the drug is an indispensable prerequisite for the performance of another service covered by the OKP and this is clearly the primary objective. The health insurer determines the amount of reimbursement after consultation with the marketing authorization holder.
Consequently, the reimbursement policy for biosimilar medicine does not differ to the requirements for the original drug.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
No, since reimbursement policy for biosimilar medicine does not differ to the requirements for the original drug (see question 8).
10. What is the legal framework for biosimilar medicines prescribing (clinical decision maker) and dispensing (pharmacy level, hospital or retail)? Is this any different to the requirements for the original Biologics drug?
The legal framework for biosimilar medicine prescribing does not differ to the requirements for the original drug. However, intra-organizational guidelines and policies in hospitals can influence prescribing behaviour for biosimilar products. There are only a few hospitals which have clear guidelines or statements from the hospital management on the use of biosimilars. Most hospitals in Switzerland do not currently have any guidelines from the management on the use of biosimilars. In Switzerland, the format of the medical indication dominates, i.e. the prescribing physicians decide on the therapy and not cost specifications by the management.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
In Switzerland, the automatic substitution of biologics (physician-led switching and/or pharmacy-level substitution) is not allowed as the substitution paragraph in the Health Insurance Act refers only to chemical drugs and generics (Art. 52a HIA).
12. What are the post – authorisation requirements (including pharmacovigilance, risk management plans, post-approval studies) for biosimilar medicines? Is this any different to the requirements for the original Biologics drug?
Regulatory documents must be continuously updated, and the use of a drug must be constantly monitored. The pharmaceutical company has a duty to notify the competent authorities of all changes that affect the granted marketing authorization. Depending on the scope of the changes, they may have to be approved by the authorities. Simple changes that only require notification are, for example, administrative changes at the manufacturer or minor changes in the manufacturing process. Changes to the dose, the dosage form or the form of application, for example, require approval. Any change to the summary of product characteristics also requires approval. Furthermore, the pharmaceutical company is obliged to collect and evaluate information on adverse drug reactions even after marketing authorization has been granted. Reports must be submitted to the regulatory authority at specified intervals and in the case of serious, unexpected cases of adverse drug reactions also within short deadlines. Continuous monitoring is so important as it is not possible to detect rare or very rare side effects in clinical trials with only a few thousand patients.
Consequently, the post-authorisation requirement for biosimilars do not differ to the requirements for the original biologics drug.
13. Are there specific policies and requirements for labelling biosimilar medicines in the event of second medical use patents? Is this any different from the requirements for the original Biologic drug?
In general, the information on the drug package serves to ensure that a drug is recognized as such as unmistakably as possible. Every medicine package must, therefore, be provided with prescribed information. This includes the brand name of the drug and its active ingredient as well as some important information on safety and proper storage. Each package also contains a patient information leaflet in the three (out of four) national languages. It provides information on the purpose, correct use and symptoms of any undesirable effects of the drug.
Moreover, the product information for a biosimilar is not an exact copy of that for the original biologics drug. However, all appropriate sections of the product information text for the biosimilar must be identical to the corresponding sections of the product information for the original biologics drug. Since a biosimilar does not need to have all the indications of the original biologics drug, the information for healthcare professionals may differ in the “Indications / usage” section, for example.
14. Have there been any significant legal/judicial developments in relation to biosimilars in your country? (Including but not limited to IP, procurement, competition, misleading information campaign, access to reference comparator product)
Switzerland ratified its first legislations concerning biosimilars in 2008. Since then a few new regulations have been ratified. However, there are no significant legal/judicial developments in relation to biosimilars from the past year.
15. Are there proposals for reform or significant change to the legal, regulatory, procurement of biosimilars? If yes, when are they likely to come into force?
Under the current Swiss Patent Act (PatA), a Supplementary Protection Certificate (SPC) grants the same rights as the corresponding basic patent and is subject to the same restrictions. A SPC, thus, protects all types of commercial use of the protected medicinal product, including manufacturing, storage, offering, market placement, import, export and transit. However, these do not include the manufacture of generics or biosimilars for export purposes or the stockpiling of generics or biosimilars for market entry in Switzerland immediately after expiry of the SPC. In other words: Under applicable law, no SPC manufacturing waiver is available to Swiss generic/biosimilars manufacturers.
Initiated by the parliamentary request «SPC-Waiver: Switzerland also needs a solution to maintain the competitiveness of the generics industry» of 12 June, the Federal Council expressed its opinion for the first time on 17 July 2019 on the introduction of an SPC Manufacturing Waiver in Switzerland. The Federal Council announced that it would analyse the advantages and disadvantages of introducing a manufacturing waiver for Switzerland and then decide on the next steps. As the competent authority, the Federal Department of Justice and Police and in particular the Swiss Federal Institute of Intellectual Property are responsible for this matter.
In principle, the Federal Council will endeavour to bring the Swiss regulations on SPC into line with European law. In view of the vastly controversial discussions in the EU that preceded the introduction of the SPC Manufacturing Waiver, the Federal Council may be inclined to wait for the first experiences with the SPC Manufacturing Waiver in the EU and, based thereon, to decide on its possible implementation. The parliamentary procedure for the legislative amendment required to introduce the SPC Manufacturing Waiver will also take some time.