Amendments to the Federal Law On Circulation of Pharmaceuticals

Transcription

1 Amendments to the Federal Law On Circulation of Pharmaceuticals March 2015 / Issue No. 40 [111] What s new? The Federal Law On amendment of the Federal Law On circulation of pharmaceuticals No. 429-FZ (hereinafter the Law No. 429-FZ ) was signed on 22 December This legal act introduces significant amendments into the Federal Law On circulation of pharmaceuticals No. 61-FZ dated 12 April 2010 (hereinafter the Law ). The key amendments include the following: introduction of new definitions, as well as adjusting of existing definitions, including, inter alia, introduction of such definitions with respect to pharmaceuticals as orphan pharmaceutical, biologic pharmaceutical, biosimilar, interchangeable pharmaceutical, introducing a definition of a holder or owner of a registration certificate (Marketing Authorisation Holder); separation of clinical trials from the state registration of pharmaceuticals along with adjustment of the mentioned procedures; establishing new grounds for cancellation of pharmaceutical s state registration; establishment of a possibility to provide scientific consultations upon request from a participant of pharmaceuticals turnover; introduction of requirements on development and enactment of good practices rules; establishment of procedure for determination of pharmaceuticals interchangeability; imposition of responsibility and liability on a holder or owner of a registration certificate (Marketing Authorisation Holder); amendment of rules for the state registration of maximum selling prices for pharmaceuticals included into the List of essential and vitally important medicines (hereinafter EDL pharmaceuticals ); establishment of potential possibility for pretrial closing of websites containing information on distant retail of pharmaceuticals. Apart from separate provisions the amendments to the Law shall enter into force on 01 July

2 New definitions, as well as adjustment of the existing definitions The Law No. 429-FZ introduces a number of new definitions into the Law including, inter alia, such definitions as orphan pharmaceutical, biologic pharmaceutical, biotechnical pharmaceutical, gene-therapy pharmaceutical, bio-analogous (biosimilar) pharmaceutical, homeopathic pharmaceutical, etc. Under the Law a biologic pharmaceutical is defined as pharmaceutical which active ingredient is produced or derived from biological sources and which requires a combination of biological and physicochemical methods for evaluating of properties and quality. Bio-analogous (biosimilar) pharmaceutical is defined as biologic pharmaceutical which quality, effectiveness and safety parameters are similar to those of the reference (original) biologic pharmaceutical, in the same dosage form and that has an identical form of consumption. It is worth mentioning that the Law differentiates terms of biosimilar and generic pharmaceutical for the first time. Also the Law introduces a new term of interchangeable pharmaceutical which is defined as a pharmaceutical which therapeutic equivalence or bio-equivalence with respect to a reference pharmaceutical has been confirmed, and which qualitative and quantitative composition of active ingredients, composition of excipients, dosage form and form of consumption are equivalent to those of the reference pharmaceutical. Furthermore, a term of a holder or owner of a registration certificate (Marketing Authorisation Holder) is also set. At the same time some definitions that are used under the Law by the moment are amended. Thus, starting from 01 July 2015 instead of original pharmaceutical a term reference pharmaceutical shall be applied which is defined as pharmaceutical registered in Russia for the first time, which quality, effectiveness and safety are confirmed by the results of preclinical and clinical trials and which is used for assessment of bioequivalence, therapeutic equivalence, quality, effectiveness and safety of generic or bio-analogous (biosimilar) pharmaceutical. Separation of clinical trials from the state registration of pharmaceuticals along with adjustment of the mentioned procedures Further to the frequent recommendations from pharmaceutical community the legislator separates a procedure of clinical trials from the state registration of pharmaceuticals, which shall be performed as independent procedures to be initiated under separate applications. Therefore, it will be possible to conduct clinical trials in the absence of an application for the state registration of respective pharmaceutical. With that several amendments are additionally introduced in the procedures of clinical trials and state registration. In particular, the following amendments are introduced with respect to the state registration: a time period for the state registration of a pharmaceutical is reduced from 210 to 160 working days; an accelerated registration procedure is prescribed for orphan pharmaceuticals, first three registered in Russia generic pharmaceuticals (at the same time, this procedure cannot be applied to biosimilar pharmaceuticals, as well as forth and any subsequent generic pharmaceuticals registered in Russia), as well as for pharmaceuticals aimed for consumption solely by children of minority age; a time period for an accelerated expert examination of pharmaceuticals is increased from 60 to 80 working days; it is permitted to provide results of preclinical and clinical trials of a pharmaceutical for medical treatment, performed abroad in accordance with the rules of good laboratory and good clinical practices, for the state registration of orphan pharmaceuticals; manufacturers of generic pharmaceuticals are eligible to file an application for the state registration of a pharmaceutical upon expiration of 4 years period from a date of the state registration of a reference pharmaceutical in Russia; manufacturers of biosimilar pharmaceuticals - upon expiration of 3 years period from a date of the state registration of a reference pharmaceutical in Russia (the amendments mentioned in this paragraph shall enter into force on 01 January 2016);

3 the detailed requirements are provided for content and completeness of each section of a registration dossier which shall be prepared as a common technical document for pharmaceuticals for medical treatment starting from 01 January 2016 under a template to be adopted by the Russian Ministry of Health (hereinafter the MoH ); along with an application for the state registration a manufacturer shall provide for the state registration of pharmaceuticals manufactured abroad an explicit statement of consent to be inspected on compliance to GMP. Some amendments are also introduced with respect to clinical trials, inter alia: further to the recommendations from pharmaceutical community the Law adjusts requirements to the term of professional experience from 5 to 3 years for an investigator responsible for performance of clinical trials of pharmaceuticals for medical treatment; clinical trials with respect to a pharmaceutical for medical treatment may be suspended or even terminated in case of conclusion on their performance with violation of GCP rules as a result of an audit of one or more medical organisations conducting clinical trials. Additional grounds for cancellation of pharmaceutical s state registration The Law No. 429-FZ provides additional grounds for cancellation of pharmaceutical s state registration, including: absence in commercial turnover within Russia for 3 years or for a longer period; nonfulfillment of measures on ensuring safety of pharmaceuticals by a holder or owner of a registration certificate (MAH) or other person authorised by the MAH; refusal of a MAH or other person authorised by the MAH to amend instructions on application of pharmaceutical as provided by the Law. Establishment of a possibility to provide scientific consultations upon request from a participant of pharmaceuticals turnover The Law No. 429-FZ prescribes a possibility for participants of pharmaceuticals turnover to obtain for a fee a scientific consultation from the MoH with respect to the issues associated with pre-clinical and clinical trials, expert examination of quality, effectiveness and safety of pharmaceuticals, state registration of pharmaceuticals. The consulting shall be performed with involvement of subordinated federal state budget institutions of the MoH which do not participate in expert examination of pharmaceuticals quality under the state registration procedure. Information on the mentioned consulting shall be published on the official website of the MoH. Introduction of requirements on development and enactment of good practices rules The Law No. 429-FZ provides the necessity for adoption at the federal level of the rules of good laboratory practice (GLP), good clinical practice (GCP), good manufacturing practice (GMP), good storage and transportation practice, good distribution practice (GDP), good pharmacy practice (GPP) and good pharmacovigilance practice (GVP) with respect to pharmaceuticals for medical treatment. The compliance with these practices becomes mandatory for all parties involved in the relevant types of activities. Establishment of procedure for determination of pharmaceuticals interchangeability Determination of pharmaceuticals interchangeability may be of importance for application of competition law (for determination of a goods market), as well as for application of the legislation on contractual system in the sphere of public procurements for state and municipal purposes. Under the amendments introduced by the Law No. 429-FZ interchangeability of pharmaceuticals for medical treatment shall be determined by a commission of experts during the pharmaceutical s state registration under a procedure established by the Russian Government on a basis of the following criteria:

4 equivalence (comparability - for biosimilars) of qualitative and quantitative characteristics for pharmaceutical substances; equivalence of a dosage form; equivalence or comparability of a composition of excipients; identity of the forms of consumption and application; absence of clinically relevant differences within examination of bioequivalence or therapeutic equivalence; compliance of a manufacturer with the requirements of GMP. The Law No. 429-FZ prescribes a set of provisions with respect to interchangeability for a transitional period: information on interchangeability of pharmaceuticals for medical treatment shall be introduced into the State register of pharmaceuticals as of 01 January 2018; determination of interchangeability with respect to pharmaceuticals for medical treatment registered before the entry of the Law No. 429-FZ into force shall be performed until 31 December 2017; the holders or owners of registration certificates for pharmaceuticals (MAH) may file an application for determination of interchangeability of pharmaceuticals for medical treatment before 31 December 2016; the results of determining interchangeability of pharmaceuticals for medical treatment could be applied as of 01 January Imposition of responsibility and liability on a holder or owner of a registration certificate (MAH) The Law No. 429-FZ introduces at the legislative level an important for the industry term of a holder or owner of a registration certificate (MAH) for the first time. The mentioned definition refers to a developer of a pharmaceutical, a manufacturer of pharmaceuticals or other legal entity that is entitled to hold a registration certificate and responsible for quality, effectiveness and safety of the pharmaceutical. According to the amendments introduced into the Law a holder or owner of a registration certificate (MAH) or other legal entities authorised by them are responsible within assurance of pharmaceuticals safety to receive, record, process, analyse and store information on side effects, adverse reactions, serious adverse and unexpected adverse reactions within application of pharmaceuticals, the peculiarities of pharmaceuticals interactions with other pharmaceuticals, individual intolerance, as well as about other facts and circumstances that may threat life or health of a person or an animal or may change the expected balance of benefits to the possible risk of pharmaceuticals use, that can be received by them from the participants of pharmaceuticals turnover and the state authorities. Upon reveal of information on serious adverse reactions, and unexpected adverse reactions within application of a pharmaceutical, the peculiarities of a pharmaceutical interactions with other pharmaceuticals, individual intolerance, as well as about other facts and circumstances that may change the expected balance of benefits to the possible risk of pharmaceuticals use, a holder or owner of a registration certificate or other legal entities authorised by them shall undertake measures aimed at elimination of negative consequences from application of such pharmaceutical, mitigation of harm that may be caused to life or health, as well as additionally collect information on effectiveness and safety of such pharmaceutical. Failure to report or suppression of the mentioned information entails imposition of liability under the legislation of the Russian Federation on a holder or owner of a registration certificate. Violation of the mentioned requirements may also entail suspension for application of the pharmaceutical. Moreover, a holder or owner of a registration certificate for a pharmaceutical is obliged to provide a report outlining the results of performed pharmacovigilance with the competent federal executive agency authorised for implementation of control (supervision) in sphere of healthcare (Roszdravnadzor of Russia) in every six months within two years after the state registration of the pharmaceutical in Russia, once a year within subsequent three years, and afterwards - once in five years (amendment specified in this paragraph enters into force on 1 January 2016). The Law No. 429-FZ also stipulates that a holder or owner of a registration certificate for a biotechnological or an orphan

5 pharmaceutical in return for a fee is obliged to provide applicants with samples of a reference pharmaceutical for performance of clinic trials. Price of a sample for a reference EDL pharmaceutical shall not exceed the maximum selling price registered for the reference pharmaceutical or price of the pharmaceutical in a country of a manufacturer (provisions of the Law which set these obligations also come into effect on 1 January 2016). State registration of maximum selling prices for EDL pharmaceuticals The Law No. 429-FZ admits a possibility of reregistration of the maximum selling prices for EDL pharmaceutical for all manufacturers, by excluding from the respective legal provision of a reference on granting such right to Russian manufacturers. At the same time, foreign manufacturers may obtain a right to re-register maximum selling prices for EDL pharmaceuticals only if respective provisions are duplicated in the subordinate regulations that establish procedure of price registration. The list of criteria that shall be applied under the state registration of the maximum selling prices becomes inexplicit and less detailed. With that, the Russian Government is provided with the authority to establish the procedure and particularities of the price registration under the inexplicit list of criteria that ultimately provides it with a significant freedom within the process of the price regulation. The manufacturers are expressly prohibited to sell EDL pharmaceuticals for a price exceeding the maximum registered prices. This prohibition is established at the legislative level for the first time (previously, this prohibition was assumed and, in contrast to price mark-ups, was not clearly established at the statutory level). It shall be mentioned that the abovementioned authority to establish the procedure and particularities of the price registration for EDL pharmaceuticals may be provided to the Russian Government even before 1 July Currently the Russian Parliament considers a draft law No This draft law already adopted by the State Duma (lower chamber of the Parliament) in a third hearing on 20 February 2015 provides introduction of amendments into article 61 of the Law identical to amendments provided by the Law No. 429-FZ. Under the draft law these amendments in part of vesting the Russian Government with the mentioned authority shall enter into force already from 1 March 2015 (while other amendments in article 61 of the Law shall enter into force from 1 July 2015). Selective quality control of pharmaceuticals The Law No. 429-FZ provides for selective quality control of pharmaceuticals to be carried out by the federal controlling authority (Roszdravnadzor of Russia). Earlier a similar control has been carried out on the basis of the subordinate legal act issued by Roszdravnadzor of Russia. The control provided by the Law No. 429-FZ includes the following: processing of data which is subject to mandatory reporting by participants of pharmaceuticals turnover; selection of samples of pharmaceuticals from participants of their turnover for the test purposes; adoption of a decision on further civil circulation of a pharmaceutical (or on suspension of such circulation) on the basis of tests results; adoption of a decision on a transfer of a pharmaceutical to multiple selective quality control in case of repeated detection of a quality incompliance of a pharmaceutical with the established requirements and (if necessary) on an audit of a participant of pharmaceuticals turnover. The expenses connected with a multiple selective quality control of pharmaceuticals shall be incurred by their manufacturer or by a holder or owner of a registration certificate. In case of a failure to fulfill instructions of Roszdravnadzor of Russia issued on a basis of selective quality control of pharmaceuticals, this authority is entitled to decide on suspension of such pharmaceuticals application. Pharmacovigilance The liability for the quality, effectiveness and safety of pharmaceuticals is additionally imposed on a holder or owner of a registration certificate (MAH). The MAH, as well as legal entities in a name of which permissions for conducting clinical trials are issued, shall be subject to responsibilities in the field of a pharmacovigilance described above in the section Imposition of responsibility and

6 liability on a holder or owner of a registration certificate (MAH). Pretrial closing of websites containing information on distant retail of pharmaceuticals The Law No. 429-FZ sets potential possibility for pretrial closing of websites which contain information on distant retail of pharmaceuticals, an offer for distant acquisition, distant delivery and (or) distant transfer to an individual of pharmaceuticals, narcotic and psychotropic pharmaceuticals, except for the cases expressly allowed by the Russian Government (the mentioned action on closing of websites is assigned to the competence of federal executive authorities in circulation of pharmaceuticals). What's next? The MoH has published notifications on development of a Resolution of the Russian Government and series of orders of the MoH aimed at implementation of the amendments introduced by the Law No. 429-FZ. The respective notifications are posted on the united portal for publishing information on development of draft regulations by the federal executive authorities and the results of their public discussion. The time periods for public discussions of the mentioned notifications vary and at present a number of the notifications have already completed this stage, while others are still undergoing public discussions. According to information posted on the mentioned portal, the MoH plans to develop documents (drafts of resolutions of the Russian Government and orders of the MoH) with respect to the following issues: state regulation of prices for EDL pharmaceuticals (resolution of the Russian Government); rules of providing scientific consultations and methodology of determining fees for their provision; procedure of generating a registration dossier for a pharmaceutical and requirements to the documents included in respective dossier; adopting a form of a common technical document; requirements to a volume of information to be provided in a registration dossier for separate types of pharmaceuticals for medical treatment; rules of providing documents that constitute a registration dossier of pharmaceuticals for medical treatment; volume of information necessary for generating documentation on clinical trials under the state registration of pharmaceuticals for medical treatment; classification of amendments introduced into documentation contained in a registration dossier for a registered pharmaceutical; rules for expert examination of pharmaceuticals and particularities of performing expert examination with respect to separate types of pharmaceuticals; rules of conducting trials for attesting an absence of influence of excipients or auxiliary tools on safety and (or) effectiveness of pharmaceuticals for medical treatment; rules of good clinical practice (GCP), good laboratory practice (GLP), good pharmacovigilance practice (GVP), good storage and transportation practice, good distribution practice (GDP), good pharmacy practice (GPP) with respect to pharmaceuticals for medical treatment; requirements to application instructions for pharmaceuticals for medical treatment; list of dosage forms names, the rules of a rational choice of a name for a pharmaceutical for medical treatment; introduction of amendments to the current procedures of monitoring safety of pharmaceuticals for medical treatment (established under the Order of the MoH No. 757N dated 26 August 2010); procedures of receiving, recording, processing, analysis and storage of information on side effects and other consequences of pharmaceuticals application by a holder or owner of a registration certificate (MAH); form of a document containing results of monitoring effectiveness and safety of a pharmaceutical conducted by a holder or owner of a registration certificate (MAH) for a pharmaceutical; procedure of pharmacovigilance; procedure of selective quality control of pharmaceuticals.

7 According to internet resources an expected term of entering into force of the regulations is 1 July 2015 for the Resolution of the Russian Government and third quarter of for the regulations of the MoH. How can we assist you? Taking into account our more than 10 years experience in consulting our clients on the issues associated with the legislation on circulation of pharmaceuticals we will be pleased to discuss any questions that you may have with respect to application of the Law No. 429-FZ and subordinate acts that are being issued under the mentioned law, to review agreements and local regulations currently used in your company in terms of compliance to the mentioned statutory acts, as well as to propose solutions tailored with your business purposes in order to mitigate potential risks.

8 Contacts Yana Zoloeva PwC Legal, Partner Legal Practice Leader +7 (495) Andrey Odabashian PwC Legal, Senior Associate Head of Group on rendering legal services to pharmaceutical companies +7 (495) , ext Alina Lavrentieva Partner Head of PwC Practice on rendering services to pharmaceutical companies +7 (495) Anna Ruviskaya Senior Manager Practice on rendering tax services to pharmaceutical companies +7 (495) Ilya Solomatin PwC Legal, Associate Group on rendering legal services to pharmaceutical companies +7 (495) , ext All rights reserved. PwC and PricewaterhouseCoopers refer to OOO PwC Legal and OOO PwC Advisory or, as the context requires, other member firms of PricewaterhouseCoopers International Limited, each of which is a separate and independent legal entity. The information contained in this flash report does not constitute professional advice. PwC is not responsible for any damages that may be incurred by any parties if their actions or failure to act were based on their reading of this flash report. For assistance with specific questions, we advise that you contact a PwC professional in the relevant line of service.