Biosimilars and Biologics
All legal aspects surrounding localization in Bulgaria. Prepared in association with Kinstellar and PharmDedict, this is an extract from The Pharma Legal Handbook: Bulgaria, available to purchase here for GBP 75.
1. Are biosimilar medicines considered the same as generic medicines in your country?
In order to be considered generic biosimilar medicines shall fulfill the requirements for categorizing a product as generic, namely: Generic medicinal product shall be a medicinal product of the same qualitative and quantitative composition in terms of its active substances and of the same pharmaceutical form as its reference medicinal product (e.g. the biological product), and its bioequivalence with the reference medicinal product has been substantiated through suitable bioavailability tests.
If the biosimilar medicine could not be considered generic, the latter would be categorised as new active substance.
2. Are all biologic medicines, including biosimilar medicines, patentable in your country?
In order to be patentable in Bulgaria, a biological medicine shall be new, have an inventive step and be industrially applicable. A biosimilar medicine may also be patentable, to the extent it meets the above general requirements.
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 general rules and procedures of the MPHMA and Ordinance No. 27 of 15.06.2007 on the requirements to the data and documentation for authorisation for use and registration of medicinal products (“Ordinance No. 27”) for marketing authorisation of medicinal products apply also to biosimilar medicines. In case the biosimilar medicine meets the criteria for a generic drug (please see p.1 above), the process may be shorter, as the presentation of pre-clinical and clinical study results is not required, if the so-called “data exclusivity” period has expired. However, where a biosimilar medicinal product does not meet the requirements for qualification as a generic medicinal product, due to a difference in the manufacturing process or to different starting materials compared to the reference product, or due to any other reasons, the applicant has to submit to the Bulgarian Drugs Agency the results from the required pre-clinical and/or clinical trials associated with those requirements.
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?
Please see p. 3 above.
5. What are the requirements for the choice of the reference comparator product?
By choosing the reference comparator products the existence of bioequivalence and bioavailability should be assessed.
According to the MPHMA bioequivalence shall be deemed present where medicinal products are pharmaceutically equivalent or pharmaceutical alternatives, and where their bioavailability after administration in the same molar dose is similar to the extent that their effect in terms of efficacy and safety is substantively similar.
Bioavailability is the speed and level at which the active substance or its therapeutically active part are absorbed from the pharmaceutical form and become available at the location of activity. When the medicinal substance is intended to have a systemic therapeutic effect, bioavailability shall mean the speed and level at which the medicinal substance or its therapeutically active part are released from the pharmaceutical form and pass into the general circulation.
The existence of bioequivalence and bioavailability is assessed through clinical trials.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
The comparator product may be sourced from another Member State. In such case the Bulgarian Drug Agency requests from the regulatory body of the Member State, where the reference product is authorised, information about the product’s market authorisation, the quantitative and qualitative composition of the reference product and, if necessary, additional documentation.
7. How are the prices of biosimilar medicines regulated? Is this any different from the requirements for the original Biologics drug?
There are no special rules for regulation of the prices of biological or biosimilar products. In general, after its market authorisation the National Council on Prices and Reimbursement of Medicinal Products (“NCPRMP”) regulates the price of a medicinal product depending on its designation:
- To be used only upon medical prescription;
- To be used without medical prescription as OTC product;
- To be covered by state funds through its inclusion in the Positive Drug List (“PDL”).
In Bulgaria at current date biosimilar and biological products have received market authorisation and price regulation as products to be used upon medical prescription and products covered by state funds through their inclusion in the PDL.
8. What is the reimbursement policy for biosimilar medicine? Is this any different from the requirements for the original Biologic drug?
In order to be included in the PDL and reimbursed, a biosimilar medicine should have a manufacturer price that does not exceed 70% of the price of the originator reference product (if the biosimilar product meets the criteria for a generic product) or 80% of the price of the originator reference product (if the biosimilar product does not meet the criteria for a generic product).
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
So far, biosimilar competition did not have any material impact on the reimbursement policy of the originator reference products.
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?
There is no special legal framework regulating biosimilar and biological medicines prescription and dispensing. The general legal framework applicable to prescription and dispensing of medicinal products applies also to biosimilar and biological medicines.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
Prescription of biological and biosimilar products may be done by trade name rather than by international non-proprietary name. Changes to the treatment may be done only by the clinical decision maker. Where the prescription contains the specific trade name of the product (which may be the case of biological and biosimilar products), pharmacies are obliged to dispense the specific product and may not provide substitutes.
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?
There are no special post – authorisation requirements for biosimilar and biological products.
As a general rule, after the authorisation the BDA may request the holder of the authorisation to conduct post-marketing study for the product’s safety or efficiency, if there are concerns or lack information with regard thereto.
Any changes with regard to the product occurring post-authorisation should be approved by the BDA.
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?
No special policies and requirements with regard to biosimilar and biological products labelling have been introduced under Bulgarian law.
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 significant legal/judicial developments in relation to biosimilars have been introduced in Bulgaria.
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?
No proposals for reform or significant change to the regulation of biosimilars in Bulgaria have been introduced.