Biosimilars & Biologics
Key legal info on biosimilars & biologics in Portugal. Prepared in association with Cuatrecasas, a leading Iberian law firm, this is an extract from The Pharma Legal Handbook: Portugal, available to purchase here for GBP 99.
1. Are biosimilar medicines considered the same as generic medicines in your country?
Biosimilar medicines are defined by exclusion, i.e. a biosimilar medicine is a biological medicine which does not fulfil the conditions of the definition of a generic medicine (amongst other, because of differences related to the raw materials or to the manufacturing processes). Nevertheless, their regulation is similar to generic medicines in other regards.
2. Are all biologic medicines, including biosimilar medicines patentable in your country?
Biologic medicines are patentable. Biosimilar medicines however cannot be patented since according to the Industrial Property Code pharmaceutical products may only be patented provided that they are new, inventive and have an industrial applicability.
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?
According to the Medicinal Products Act, biosimilar medicines follow the same authorization procedure to obtain a marketing authorization for generic medicines, although with some adaptions.
The most relevant difference is that for the obtainment of a marketing authorization of a biosimilar medicine, it is necessary to provide results of appropriate pre-clinical or clinical trials related to the conditions that determine that the medicine does not fit the definition of a generic medicine (for example, related to the raw materials or manufacturing processes). However it is not necessary to present results of other tests and trials related to the reference medicinal product.
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?
Besides the normal data required to obtain approval for a drug there are some special requirements for biologics drugs including biosimilar drugs, as stated above. These are provided in Annex I of Decree-Law 176/2006.
For example, it may be necessary to present additional data (e.g. the toxicological and clinical profile) if, based on the information already provided for generic medicines, it is not possible to demonstrate the similar nature between two biologic medicines.
In principle, the requirements are the same for biologic and biosimilar drugs, whereby the data to be provided is established on a case-by-case basis. However, if the biologic drug has more than one therapeutic indication, the efficacy and safety of the biosimilar medicinal product must be justified or, if necessary, demonstrated separately for each of the claimed indications.
If the biologic medicine is a plasma-derived medicinal product, the required data includes information regarding the basic substances and raw materials used. In these cases, a Plasma Master File (PMF) may be used.
5. What are the requirements for the choice of the reference comparator product?
Other than the general requirements (e.g. demonstrated bioequivalence to the reference biologic medicinal product, same pharmaceutical form, etc.), there are no specific requirements foreseen in Portuguese law.
For the purposes of prior evaluation agreements and reimbursement matters, medicines (including biosimilar and biologic medicines) must be subjected to a pharmacoeconomic and pharmacotherapeutic evaluation.
According to Ministerial Order no. 391/2019, of 30 October and Infarmed’s methodology instructions, the pharmacoeconomic evaluation to be made should be based on a comparison between the biosimilar/biologic medicine and all other options relevant to the disease or clinical condition in question (regardless of its efficacy levels), therefore the choice of comparator is very comprehensive for these purposes. The most efficient alternative to the biosimilar/biologic medicine is the one used to carry out the economic evaluation.
As for the pharmacotherapeutic evaluation, the comparator of the biologic/biosimilar product must be:
- Commonly used in clinical practice;
- Validated by scientific evidence for the indication/population in question, including regarding its efficacy and safety;
- The dosage and administration indications of the comparator must be in accordance with the summary of characteristics of the medicine;
- Covered by a financing decision, marketed and have a reported consumption.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
The requirements are the same whether the comparator product is from Portugal or from another regulatory jurisdiction.
However, for the purposes of prior evaluation agreements and reimbursement matters and underlying the economic evaluation, only comparators available in Portugal shall be used.
7. How are the prices of biosimilar medicines regulated? Is this any different to the requirements for the original Biologics drug?
The System of Assessment of Health Technologies (SiNATS), created by the Decree-Law 97/2015, regulates the pricing of medicines.
Biologic or biosimilar medicines do not follow a specific regime for the determination of their prices, therefore, if the biologic or biosimilar medicine is reimbursable under the applicable law, it may be subject to the regime of maximum prices as any other medicinal product.
8. What is the reimbursement policy for biosimilar medicine? Is this any different to the requirements for the original Biologics drug?
Biosimilar medicines benefit from the reimbursement regime applicable to their reference biological medicine, without prejudice to any necessary adaptations.
If the biosimilar medicine is part of a homogenous group of biosimilar medicines, the maximum retail price (“MRP”) of new biosimilar medicine to be reimbursed must be lower than the lowest priced biosimilar medicine, it being necessary that the lowest priced biosimilar medicine has a certain percentage of the market share of the medicines of the homogeneous group. Said percentage, as well as the margin for the MRP, are defined by the government on a case by case basis.
When the biosimilar medicine is not part of a homogeneous group, the MRP of the biosimilar drug may not be higher than 80% of the MRP of the reference biologic drug.
Moreover, some biologic drugs are subject to exceptional regimes of reimbursements, where the reimbursement fee is of 100% (Ordinances no. 48/2016 and 281/2017).
As for the prior evaluation agreements for biosimilar medicines, the economic advantage to be taken into account shall correspond to at least 20% of the direct price of the reference biological medicine.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
Biosimilar competition may impact its own reimbursement policy and/or pricing regime, but not of the reference product.
If there is a biosimilar medicine under a given International Non-Proprietary Name with at least 5 % market share of the respective active substance, the MRP of the biosimilar medicine may not be more than 70% of the MRP of the reference biologic medicine.
As for the prior evaluation agreements, the economic advantage to be taken into account must correspond to at least 30% of the direct price of the reference biological medicine if there is a biosimilar medicine under a given International Non-Proprietary Name with at least 5 % market share of the respective active substance.
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 prescription and dispensing of the biosimilar medicines specified in Ordinance 48/2016 can only be made in specialized consultations for diagnosis and treatment of certain diseases, by pharmaceutical services of the hospitals of the National Health System which are recognized by the competent authorities for such purposes (Prescribing Centers for Biological Agents).
In the case of the biosimilar medicines specified in Ordinance 281/2017, these medicines may only be prescribed by medical specialists of the areas of rheumatology, internal medicine and paediatrics, but may be dispensed in all pharmacies.
Other than in these cases, no specific regime is foreseen for the prescribing and dispensing of biologic or biosimilar medicines.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
The Portuguese Medicinal Products Act and Ordinance no. 224/2015, of 27 July already foresee such a scheme, whereby the physician is obliged to reference the International Non-Proprietary Name of the active substance when prescribing a medicine, and not the commercial name of the medicine.
Therefore, when dispensing a medicine, pharmacists are obliged to inform the patient of the existence of medicines with the same active substance, pharmaceutical form, presentation and dosage of the prescribed medicine, as well as to inform of the existence of medicines that are reimbursed by the NHS and of the one with the lowest price available in the market.
The patient is free to choose which medicine to acquire, except for the cases when the physician has indicated in the prescription the technical reasons (exclusively the ones provided for in the law) which impede the substitution of the medicine that was prescribed with a commercial denomination for another medicine.
Other than this, the physician may only indicate the commercial name of the medicine when prescribing it if the medicine is not subject to reimbursement by the State, but even then, upon dispensing of the medicines, the pharmacist must present the patient with other viable options as stated above, and the patient is free to choose which medicine to buy.
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 is a national pharmacovigilance system managed by Infarmed. The holder of the marketing authorization shall implement and maintain an internal pharmacovigilance system following the same structure and requirements of the national system, implementing risk management plans and conducting post-approval studies. The holder of the marketing authorization shall also appoint one person responsible for the pharmacovigilance and make available all the necessary documents for Infarmed regarding these matters.
These requirements as with any other medicinal products, and are also the same for biologic and biosimilar medicinal products.
More specifically, the risk management plan of the biosimilar medicinal product shall take into account the security profile of the reference biologic medicinal product. Moreover, it is especially important that any notification of an adverse event includes a clear identification of the medicinal product and its batch (be it biosimilar or biological).
13. Are there specific policies and requirements in terms of biosimilar medicines labelling in the event of second medical use patents? Is this any different to the requirements for the original Biologics drug?
There are no specific requirements foreseen in Portuguese 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)
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?