Biosimilars & Biologics
Biosimilars & biologics in Russia – a comprehensive legal overview. Prepared in association with Lidings, a leading global law firm, this is an extract from The Pharma Legal Handbook: Russia, available to purchase here for USD 99.
1. Are biosimilar medicines considered the same as generic medicines in your country?
Biosimilar drugs are not the same as generic drugs in Russia. A biosimilar drug cannot be a copy of the original biological drug, as in respect of a biosimilar drug it can neither be proved nor confirmed the full similarity of its effect on a human. Biosimilar can only be similar in certain parameters (quality, efficiency and safety) to the original biological drug, whereas a generic drug is considered to be equal to its reference drug.
2. Are all biologic medicines, including biosimilar medicines patentable in your country?
In Russia certain criteria of patentability are established that are common for all inventions and do not depend on a specific type of drug. Under the Russian Civil code a technical solution in any area is protected as an invention if it relates to a product (including a device, substance, strain of microorganisms, plant or animal cell culture) or a method (the process of carrying out actions in respect of a material object by material means), including the use of the product or method for a specific purpose. An invention is provided with legal protection if it meets the following criteria:
- Invention is novel (i.e. it is not known from the state of the art);
- Invention has an inventive step (i.e. it does not explicitly follow for a specialist from the state of the art);
- Invention is industrially applicable (i.e. it can be used in industry, agriculture, public health and other branches of the economy or in the social sphere).
Consequently, if a biologic drug (or biosimilar drug) meets the abovementioned criteria it can be patented. However, in practice, the nature of biosimilar drugs makes it hard for them to meet the novelty criterion.
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 regulatory framework is applied for biosimilars. In particular, it includes Federal law of 21.11.2011 No. 323-FZ “On fundamental healthcare principles in the Russian Federation” (“Law on fundamental healthcare principles”), Federal law of 12.04.2010 No. 61-FZ “On drugs circulation” (“Law on drug circulation”), which provisions are supplemented with the regulations adopted by the Government of the Russian Federation and Russian Ministry of Healthcare (“Minzdrav”) (including, inter alia, “Administrative regulations of the Russian Ministry of Healthcare on the provision of state services for the state registration of medical drugs”). In addition, some specific rules are applied, e.g. separate features of biosimilar drug’s examination at its registration are governed by “Rules of carrying out examination of medical drugs and features of examination of separate types of medical drugs (reference drugs, generic drugs, biological drugs, biosimilar drugs (biosimilars), homeopathic drugs, medicinal plant preparations, combinations of drugs)”.
A biosimilar drug may be subject to registration upon expiration of 3 years period of registration of its reference biologics drug.
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 data package required for all biological drugs in general, for the purposes of biosimilar drug registration applicant must specify the following information within the biosimilar drug registration dossiers: identification of drug’s type as a biosimilar drug and data on its reference biologics drug.
Further, during the state registration procedure (during quality examination and examination of correlation between anticipated benefits and possible risks of drug by the state institution) the authorized state institution must establish the biosimilar drug’s interchangeability considering the data obtained following the results of clinical studies on the absence of clinically significant differences in safety, efficacy and immunogenicity compared with the reference drug.
5. What are the requirements for the choice of the reference comparator product?
The reference comparator product must meet the following criteria:
• It is a biological drug registered in Russia;
• It has similar quality, efficiency and safety characteristics.
6. Can the comparator product be sourced from another regulatory jurisdiction? If yes, what are the data needed to support this approach?
A comparator product cannot be sourced from another regulatory jurisdiction since it is only allowed to use reference comparator drug that has Russian marketing authorization.
7. How are the prices of biosimilar medicines regulated? Is this any different to the requirements for the original Biologics drug?
General drug price regulating requirements are applied both to biosimilar and to biologics drugs. State regulation of drug prices is executed for drugs that are included in the List of vital essential and necessary drugs (“EDL”). For EDL drugs maximum sale prices must be submitted by the manufacturers or their authorized representatives and must be subject to state registration with Minzdrav. Purchasing price in the public procurement sector must not exceed the price calculated on the basis of such a registered price considering the relevant maximum wholesale mark-up.
In addition, the Russian Federal Antimonopoly Service (“FAS”) supervises the Russian market in general regarding monopolistically high or low prices establishment by manufacturers (including drug manufacturers) which is a violation of Russian antimonopoly laws. In its official Statement of 10.02.2016 (“Statement”) FAS clarified definitions of monopolistically high and low prices:
- Monopolistically low price of goods is the price, which is (1) below the amount necessary for the production and sale of such goods, expenses and profits; and (2) lower the price formed in competitive conditions at the comparable commodity market (if such market exists in Russia or abroad).
- Monopolistically drug high price of goods is the price, which is (1) above the amount necessary for the production and sale of such goods, expenses and profits; and (2) above the price formed in competitive conditions at the commodity market comparable in composition of buyers or sellers of goods, conditions of goods circulation, conditions of access to the commodity market, state regulation, including taxation and customs and tariff regulation (if such market exists in Russia or abroad).
In order to prevent establishing monopolistically high or low prices FAS developed certain mechanisms so that to identify timely the fact of monopolistically high or low price establishment and to take relevant prevention measures. Due to recent FAS practice, this approach is applied not only to EDL drugs but to all drugs in general.
Thus, for drug manufacturers it is recommended to establish an economically justified price that considers all pricing factors (i.e. purchase volume, forms and terms of payment, the presence of delays and arrears in payment, packing forms, etc.).
8. What is the reimbursement policy for biosimilar medicine? Is this any different to the requirements for the original Biologics drug?
Russian laws do not contain specific rules for reimbursement of expenses for biosimilars. Reimbursement of biosimilars cost for certain categories of the population is the same as for all other drugs.
At the legislative level, there is a list of groups of citizens that are entitled to receive drugs free of charge or with a 50 percent discount.
The List of drugs to provide certain categories of citizens and the EDL are established, reimbursement of the cost of drugs under these lists is at the expense of the Federal budget. Besides, there is a list of high-cost nosologic diseases. The purchase of drugs (including biosimilars) intended for the treatment of such diseases is also compensated at the expense of the Federal budget.
9. Does biosimilar competition impact the reimbursement policy of the originator reference products?
Biosimilars certainly create some competition for originator reference biologics mainly due to the fact that biosimilars are less expensive and thus their purchase is less expensive for the state.
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 are no specific requirements defining the procedure for prescribing biosimilar drugs, thus, general rules are applied.
Main laws and statutory instruments governing the procedure for drugs prescribing, including biosimilars, are as follows:
- “Procedure for drugs prescribing” (established by Minzdrav Order of 14.01.2019 No. 4n);
- “Instructions for the procedure for drugs prescribing and executing drug orders and inventory orders” (Annex No. 13 to Minzdrav Order of 12.02.2007 No. 110).
There are no specific rules for biosimilars dispensing as well. Thus, biosimilar drugs are to be dispensed on the basis of the same legal acts and according to the same rules that are established for all drugs in general.
The rules for drugs dispensing are established on the basis of the “Rules for drugs dispensing, including immunobiologicals, by pharmacy institutions, individual entrepreneurs licensed for pharmaceutical activity”, “Rules for drugs dispensing by healthcare institutions having a license for pharmaceutical activity and their separate subdivisions located in rural settlements where pharmacy institutions are absent”, etc.
11. Is the system considering physician-led switching and/or pharmacy-level substitution (without involvement of the clinical decision maker)?
The interchangeability of a drug is determined in the process of its state registration on the basis of comparison with a reference drug.
Pursuant to the Law on fundamental healthcare principles the duty to select the appropriate treatment for the patient is imposed on its attending physician. Thus, physician may prescribe a biosimilar drug instead of the original biologic drug after consultation with the patient based on a comprehensive examination of the patient, if the biosimilar drug has passed its registration procedure.
The final decision remains in the competence of the attending physician, who must act in the interests of the patient.
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?
General drugs post-authorization requirements are applied to biosimilar drugs. Each marketing authorization holder must carry out the reception, accounting, processing, analysis and storage of all notifications received about side effects, adverse reactions, serious adverse reactions with the use of drugs, about the individual intolerance, lack of efficacy of drugs, as well as about other facts and circumstances that represent a threat to life or health of a human with the use of drugs. All such notifications must be reported to state authorities.
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?
General drug labeling requirements are applied to biosimilar drugs.
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?
In August 2019 Minzdrav developed a draft law that renews procedure for determining the interchangeability of drugs. At the moment of this publication, the draft law is at the regulatory impact assessment stage.
The draft law offers extensive guidance for the determination of drug interchangeability and specifies, inter alia, that the government will have the right to establish the rules and features of determining the interchangeability of biological drugs.