Biosimilars and Biologics
The legal framework for biosimilars and biologics in Slovakian Pharma. Prepared in association with PRK Partners, a leading global law firm, this is an extract from The Pharma Legal Handbook: Slovakia, available to purchase here for GBP 75.
1. Are biosimilar medicines considered the same as generic medicines in your country?
Biosimilar medicines are not considered the same as generic medicines in Slovakia. A similar biological medicinal product, also known as “biosimilar”, is a product which is similar (not identical) to a biological medicinal product that has already been authorised in the EAA, a so-called “reference medicinal product”.
The active substance in case of biological medicinal products is made from living organisms. As a result, there may be some minor differences from the reference medicinal product; natural variability is inherent to all biological medicinal products. However, these minor differences are not clinically meaningful, i.e. no differences are expected in safety and efficacy.
2. Are all biologic medicines, including biosimilar medicines, patentable in your country?
In general, any invention that meets the requirements of novelty, inventive step and capability of industrial application can be patented under Slovak patent law. The Slovak patent law addresses also biotechnological inventions which are also patentable, even if they concern a product consisting of or containing biological material or a process by means of which biological material is produced, processed or used, including inventions which concern:
- biological material which is isolated from its natural environment or produced by means of a technical process may be the subject of an invention even if it previously occurred in nature;
- microbiological or other technical process or a product obtained by means of such a process; or
- an element isolated from the human body or otherwise produced by means of a technical process, including the sequence or partial sequence of a gene, may constitute a patentable invention, even if the structure of that element is identical to that of a natural element.
There are certain inventions which are excluded from the patentability under Slovak patent law e.g., inventions relating to the human body at various stages of development, invention which commercial use would be contrary to public policy or good manners (in particular, methods of human cloning, use of human embryo for industrial or commercial purposes).
Should the biologic medicine fulfil the statutory requirements outlined above, it should be patentable under Slovak law. Given the nature of biosimilar medicines in terms of their high similarity to biological medicinal products, their patentability seems to be rather questionable. Although a different element related to the biosimilar medicine (e.g. a difference in the production process of the biological material) can fulfil the criteria of an invention under the Slovak patent law, it should be carefully assessed from the perspective of the process of obtaining the marketing authorization during which the highly similarity of the biosimilar medicine must be proved.
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?
The Act on Medicinal Products basically states in connection with the marketing authorization of biosimilar medicines that the applicant is required to submit the results of the relevant toxicological and pharmacological test and the clinical trials related to the differences between the “reference” biological medicinal product and biosimilar medicines; it is not necessary to submit the results of toxicological and pharmacological test and the clinical trials already carried out in relation to the reference biological medicinal product.
Otherwise, there is no specific regulatory framework for the marketing authorization of biosimilar medicines in Slovakia. According to the Annex to the Regulation (EC) No. 726/2004, medicinal products developed by means of biotechnological processes and medicinal products for treating of specific diseases (e.g. auto-immune diseases), basically most of the biosimilar medicines, are authorized through the centralized procedure (the respective marketing authorization is issued by the European Commission and is valid for all EEA member states).
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?
As discussed in Answer No. 3 above, most of biosimilar medicines are authorized through the centralized procedure by the European Commission. The European Medicines Agency has issued several guidelines on biological medicinal products and Q&As to assist developers prepare marketing authorisation applications.
According to the European Medicines Agency, the development of biosimilar medicines relies heavily on comparability studies to establish (high) similarity to the reference product, whereas comparability is conceived as a stepwise process that is tailor-made for each product. When assessing the marketing authorisation applications for biosimilars, the applicants must thus mainly demonstrate this similarity through comprehensive comparability studies with the reference product.
The respective data and documentation to be provided by the applicant are specified in Directive 2001/83/EC, in particular in Annex No. 1 which is supplemented by sections containing additional special requirements for biological medicinal products (e.g. with respect to toxicological and pharmacological tests, the requirements may have to be adapted for individual biological medicinal products).
5. What are the requirements for the choice of the reference comparator product?
According to the Guideline on similar biological medicinal products of the European Medicines Agency, the reference medicinal product must be a medicinal product authorised in the EEA, on the basis of a complete dossier in accordance with the provisions of Article 8 of Directive 2001/83/EC. Further, according to the Regulation (EC) No. 726/2004, the medicinal products for human use (including the biological medicinal products) which have been authorised in accordance with the provisions of this Regulation shall benefit from an eight-year period of data exclusivity and a ten-year period of market exclusivity (this period can be extended to a maximum of 11 years).
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
The Guideline on similar biological medicinal products of the European Medicines Agency provides for an exemption in order to facilitate the global development of biological medicinal products and to avoid unnecessary repetition of clinical trials. Under this exemption, it may be possible for the applicant to compare the biological medicinal products in certain clinical studies and in in vivo non-clinical studies with 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 European Medicines Agency (e.g. ICH countries). However, it will be the applicant’s responsibility to demonstrate that the comparator authorised outside the EEA is representative of the reference product authorised in the EEA.
7. How are the prices of biosimilar medicines regulated? Is this any different from the requirements for the original Biologics drug?
There is no special legislation for the regulation of the prices of biosimilar medicines nor original biological drugs. In Slovakia, the Slovak Ministry of Health is the competent authority, among other matters, for the pricing and categorization of the medicinal products.
Under the Slovak special pricing legislation, ERP is used when setting the prices of medicinal products in order to be registered into the “List of medicinal products with officially determined price” or “List of categorized medicinal products”. Generally, the “European reference price of medicinal product” cannot be exceeded when setting the price of a medicinal product. For the calculation of the “European reference price of a medicinal product”, the average price comparison of three lowest prices in other EU countries is used.
8. What is the reimbursement policy for biosimilar medicine? Is this any different from the requirements for the original Biologic drug?
There is no special legislation for the reimbursement policy of biosimilar medicines nor original biological drugs. In Slovakia, the Slovak Ministry of Health is the competent authority, among other matters, for categorization of the medicinal products.
Medicinal products in general with officially determined price are fully reimbursable from the public health insurance system only when administered within hospital care (uninterrupted health care for more than 24 hours). In order to become (partially or fully) reimbursable from the public health insurance system also when administered within out-patient care or when dispensed by pharmacies, the respective medicinal product must be listed in the “List of categorized medicinal products”. Please also see our answer to question No. 7 above.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
As indicated our answers to questions Nos. 10 and 11 below, the biological medicinal products are practically excluded from the substitution given their nature based on similarity. Having said that, the biosimilar competition does not seem to have an impact on the reimbursement policy of the original (reference) biologicals.
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?
In general, the physician is responsible for the correct choice of the active substance or the medicinal product when prescribing a medicinal product to the patient. In case of medicinal products (fully or partially) reimbursable from the public health insurance, the physician is obliged prescribe the medicinal product by way of stating, among other details, “only” the respective active substance (without specifying the brand name of the respective medicinal product). However, the physician may also specify the brand name of the respective medicinal product, along with the specification of the respective active substance. On the pharmacy level, the pharmacist is obliged to inform the patient on the possibility of the substitution which can be dispensed based on the respective medical prescription and on the amount of the surcharge. However, this legislation does not specifically consider biological medicinal product or biosimilars.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
As specified in our answer to question No. 10 above, in Slovakia, the physician is responsible for the correct choice of the active substance or the medicinal product when prescribing a medicinal product to the patient. Further, the legal definition of the drug substitution encompasses only the medicinal products with the identical active substance, and thus it is conceived for the generic substitution. So, basically the prescription of biosimilars can be considered as physician-led switching.
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?
In Slovakia, there is basically no specific legal framework regarding the post—authorisation requirements, including pharmacovigilance, for biological medicinal products. So, the post—authorisation requirements related to “standard” medicinal products apply also on biological medicinal products, including biosimilars.
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?
All medicinal products are carefully monitored after they are placed on the EU market. In addition to such standard monitoring, the European Medicines Agency maintains a list of medicinal products that are under additional monitoring in the EU. This list includes medicinal products authorised in the EU (centrally or nationally authorised) that are being monitored particularly closely by regulatory authorities, including the Slovak State Institute for Drug Control. These medicinal products have a black inverted triangle displayed in their package leaflet and summary of product characteristics, together with a short sentence explaining what the triangle means.
The reason why these medicinal products are being monitored even more intensively then other medicinal products is that there is less information available on them than on other medicinal products (e.g., because they are new to the market or there is limited data on their long-term use). According to the European Medicines Agency, the list includes also biological medicines authorised after 1 January 2011 (it applies to all biological medicinal products including biosimilars).
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)
No, in particular due to the fact that biosimilars are rather new to the Slovak market.
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?