On 27 March 2013, the plenary session of the Riigikogu adopted an amendment to the Medicinal Products Act initiated by the Government of the Republic. In this connection, the Penal Act, Act on Narcotic Drugs and Psychotropic Substances and Precursors Thereof, and State Fees Act will also be changed. The consolidated text of the amended Medicinal Products Act was published in the State Gazette on 17 April and the Medicinal Products Act enters into force ten days after publication.
The expected impact of the amendment is, based on the transposition of Directive 2011/62/EC, prevention of falsified medicinal products. For this purpose, additional requirements and obligations have been introduced mainly for holders of activity licenses for manufacture and wholesale trade in medicinal products, holders of activity licences for pharmacy services, and the State Agency of Medicines.
New terms and requirements
Pursuant to the amendments, the term 'falsified medicinal product' is defined in the Medicinal Products Act. A falsified medicinal product is deemed to be any medicinal product with false representation of its identity (any misleading labelling, statement or information as regards the composition, content of the active ingredient, etc.), source or history (any misleading labelling, statement or information as regards the manufacturer, country of manufacture, country of origin, marketing authorisation holder, consignment documents, sales documents, quality documents, etc.). In connection with the introduction of the definition of a falsified medicinal product, the regulation of and terms used in § 194 of the Penal Code will also be harmonised.
The Medicinal Products Act clarifies the terms 'active substance and 'excipient'. An active substance is a substance or mixture of substances determinable by scientific methods which is intended for use in the manufacture or preparation in a pharmacy of a medicinal product and which becomes in the manufacturing or preparation process an active ingredient of a medicinal product for the purpose of exhibiting the effect of a medicinal product specified in § 2 (1) of the Medicinal Products Act. An excipient is a constituent which is not an active substance or packaging material.
A new term, 'advanced therapy medicinal product', was introduced. An advanced therapy medicinal product is a medicinal product or tissue engineered product designed for gene therapy or somatic cell therapy. A tissue engineered product may contain cells or tissues of human or animal origin, or both; the cells or tissues may be viable or non-viable. It may also contain additional substances, such as cellular or biological materials or chemical substances, scaffolds or matrices. An advanced therapy medicinal product, which is prepared on a non-routine basis by prescription from and the professional responsibility of a medical practitioner for an individual patient while providing in-patient health care services in Estonia, does not require a marketing authorisation. The purpose of this exception (marketing authorisation not needed) is to allow risk-based therapy in situations where a patient can be helped only with an advanced therapy technology but a medicinal product derived from such technology has not yet undergone sufficient studies and the safety, effectiveness and quality of the product have not yet been sufficiently established for it to be widely used.
The term 'brokering of medicinal products' was introduced. The term 'brokering' covers activities in relation to the sale and purchase of medicinal products used in human health care, except for wholesale distribution, that consists of negotiating independently and on behalf of another legal or natural person. A broker does not own medicinal products (does not purchase or sell medicinal products, is not the owner of the traded goods) or handle them physically but leads the parties toward the conclusion of a transaction. The brokering of medicinal products does not cover the offer of medicinal products to the public. According to the implementation provision of the Medicinal Products Act, any persons who began brokering of medicinal products before the entry into force of the Act are required to submit to the State Agency of Medicines information and documents necessary for the issue of an activity licence by 27 June 2013 at the latest.
The obligation of medicinal product packages to bear safety features was established. The safety features are the means to identify a particular package and to detect tampering of a package. Replacement of safety features without having an activity licence for manufacture of medicinal products is prohibited. The purpose of the means to identify a package is to help verify the authenticity of the medicinal product and identify each package (or put simply: such means are somewhat advanced versions of bar codes or similar codes). The purpose of the means to detect tampering of packages is to provide evidence whether a package has been previously opened or damaged (stickers closing a package, etc.).
The Act establishes regulation of a sale at a distance of medicinal products (online pharmacies). In establishing these requirements, similar principles of and similarity to dispensing of medicinal products at a conventional pharmacy were adhered to wherever possible.
The sale at a distance of medicinal products is the retail sale of medicinal products by means of information society services, i.e., a service provided in the form of economic or professional activities at the direct request of a recipient of the services where data are processed, stored and transmitted in digital form by electronic means intended for digital processing and storage of data, without the parties being simultaneously present at the same time. Information society services must be entirely transmitted, conveyed and received by electronic means of communication. Services provided by means of fax or telephone call and television or radio services are not information society services.
A holder of a general pharmacy licence may apply for the right to sell at a distance medicinal products used in human health care and over-the-counter medicinal products used in veterinary medicine. The sale of prescription medicinal products used in veterinary medicine is restricted as there are no digital prescriptions in use for veterinary purposes.
The bases of delivering medicinal products ordered by way of a distance sale were set out. For the delivery of medicinal products, a provider of pharmacy services may employ companies that provide postal or freight transport services (No license to handle medicinal products is required for mere transport). The amendment of the Act does not alter the definition of the provision of pharmacy services; hence, for providers of pharmacy services, the right of distant sale of medicinal products will not create the right to deliver medicinal products. At the same time, a holder of a pharmacy service licence is not prohibited from providing postal or freight transport services as a separate economic activity.
Where medicinal products are sold at a distance to another country of the European Economic Area, or vice versa, the medicinal product concerned must comply with the marketing authorisation of the Member State of destination. The medicinal products sold in the Member States must comply with the marketing authorisation valid in the given Member State in every aspect (incl. package labelling, package leaflets, etc.).
Pursuant to the amendment, the State Agency of Medicines is required to inform the community about risks involved in purchasing medicinal products from illegal sources. The European Commission is developing a common logo to help identify legal providers of medicinal products for distant sales; this logo would be recognisable in all the Member States and allow one to ascertain the country of location of a person offering medicinal products for distant sales.
The Act obligates the wholesale distributors and brokers to comply with good distribution practices of the European Economic Area. The Guidelines on Good Distribution Practice of Medicinal Products for Human Use have been recently updated and supplemented. Holders of manufacturing and wholesale distribution licenses are required to verify the compliance of their business partners with the requirements. Besides good manufacturing practices certificates (GMP certificates), the State Agency of Medicines will also issue certificates to wholesale distributors that certify their compliance with good distribution practices (GDP certificates). Assessment of compliance will be given after inspection of the relevant company. The Agency is required to enter the data on licenses issued for manufacturing and wholesale distribution of medicinal products and active substances in the common database of the European Union.
Clarification of and supplements to the handling requirements of medicinal products
The obligations of holders of license for manufacture of medicinal products were supplemented. The holders of such a license must ensure that the active substances of a medicinal product used in human health care have been manufactured and also distributed pursuant to good practices of the European Economic Area, for which purpose the holders are required to perform audits at the manufacturering and distribution sites. Audits by third persons may also be used; however, the manufacturer remains liable. For excipients, the manufacture of medicinal products first needs to ascertain the appropriate good manufacturing practice and then ensure that such practices are applied when producing excipients.
As of 2 July 2013, it is permitted to import active substances for manufacture of human health care medicines if accompanied by a written confirmation from the competent authority of the exporting third country which indicates that the requirements applicable to the manufacturer of the imported active substance are at least equivalent to the manufacturing practices of the Community and that the manufacturer is efficiently supervised by the competent authorities of the exporting country.
The competent authority of the exporting country also needs to confirm that, in case of non-compliance of the requirements for the manufacture of an active substance, they shall promptly notify the competent authority of the country importing the active ingredient. The written confirmationis not needed if the European Commission has entered the exporting country in a relevant list (the list referred to in Article 111b of Directive 2001/83/EC of the European Parliament and Council). The Commission publishes the list on its webpage. Exceptionally, the State Agency of Medicines may authorise the import of an active substance if it is necessary to ensure availability of medicinal products, provided that the manufacturer of the active substance has been inspected by a competent authority of a Member State and the authority has concluded that it complies with good manufacturing practices of the Community.
Manufacturers and wholesale distributors of medicinal products need to verify that the companies from which they procure an active substance are authorised for this activity in their country of location. The Stage Agency of Medicines must be notified once a year of changes in the list of imported, manufactured and distributed active substances. Any changes that may affect the quality or safety of active substances must be notified immediately.
The amendment adds veterinarians to the persons to whom holders of an activity licence for manufacture and wholesale distribution are required to disclose their sales offers and ensure the availability of the medicinal products specified in sales offers, as under § 27 (1) of the Medicinal Products Act, medicinal products may also be sold wholesale to veterinarians.
Import of investigational medicinal products has been simplified. In the past, authorisation for import (“special authorisation”) issued by the State Agency of Medicines was required to import an investigational medicinal product from other Member States and from third countries. Pursuant to the amendment, such an authorisation is needed only if an investigational medicinal product is imported outside the European Economic Area. Notification replaces application for authorisation in case of import from another Member State and export to another Member State and to a third country. This amendment simplifies the import of medicinal products used in clinical trials conducted in Estonia.
Besides the hard copy prescription data, pharmacies need to digitalise the information contained in the documents certifying the insurance coverage of the persons insured in a Member State of the European Union or European Economic Area or in the Swiss Confederation.
Beginning 1 July 2013, all pharmacies need to ensure conditions to order and dispense narcotic and psychotropic medicinal products on receipt of a prescription.
Pursuant to the previous wording of § 45 5) of the Medicinal Products Act, a pharmacy was required to ensure the availability, within a reasonable period of time, of medicinal products with marketing authorisation. Pursuant to the amendment, the provider of pharmacy services additionally needs to ensure the availability, within a reasonable period of time, of unauthorised medicinal products which have been granted an authorisation to market (sell).
Clause 45 9) of the Medicinal Products Act was updated due to amendments to the relevant provisions of the Health Insurance Act. In 2005, the methodology for calculating the reference prices of medicinal products changed and they are no longer calculated as the average of the second and third cheapest pharmaceutical preparation in the group of medicinal products with the same active ingredient and route of administration, but according to the second cheapest pharmaceutical preparation. Thus, a 'reference price' no longer covers at least two pharmaceutical preparations as it did in the past. A pharmacy needs to guarantee ‒ upon the sale of medicinal products concerning which a reference price has been established on the basis of the Health Insurance Act and a price agreement has been entered into ‒ that at least one medicinal product with the same active ingredient content is offered. This provision does not require that the pharmacies maintain the entire nomenclature of pharmaceutical preparations, concerning which a price agreement has been entered into and a reference price has been established, on their premises, but, upon procuring medicinal products with a given active ingredient and route of administration, the pharmacy must primarily procure pharmaceutical preparations concerning which a price agreement has been made.
For purposes of better understanding, the term 'authorisation for use' is replaced with the term 'authorisation to market' (sell) throughout the text of the Act. This change concerns unauthorised medicinal products which cannot be used until the State Agency of Medicines has decided, upon application submitted by a doctor, that the use of a medicinal product is justified, and further to that, the Agency has issued to the wholesale distributor a special authorisation for import and an authorisation to market (sell). The previous terminology left a misleading impression that an authorisation for use of a medicinal product is given to the importer/distributor. The definition of the term 'marketing' is set out in § 3 (2) of the Medicinal Products Act.
The cases where the State Agency of Medicines deems the use of an unauthorised medicinal product justified were clarified. In the past, the State Agency of Medicines could allow the use of an unauthorised medicinal product if there were no authorised medicinal products with the same effect or if they were unavailable. Pursuant to the amendment, the State Agency of Medicines may allow the use of an unauthorised medicinal product in cases where there are no authorised medicinal products with the same effect available or if they are not marketed in keeping with therapeutic needs, i.e., they are marketed insufficiently to cover the therapeutic needs all relevant patients in a timely fashion.
At the level of the Medicinal Products Act, besides the holder of a licence to manufacture medicinal products, the obligation was put upon the holder of a licence for wholesale trade to implement a quality system which, inter alia, provides for responsibilities, processes and risk management measures.
Clarification was provided to § 28 (8) of the Medicinal Products Act pursuant to which medicinal products may be procured from the holder of a license for pharmacy services only in the cases set out in § 45 (11) of the Medicinal Products Act and in the cases of import. Dispensing medicinal products from a general pharmacy for the purpose of wholesale is contrary to the objective of the pharmacy service (§ 29 (1) of the Medicinal Products Act), the latter being the retail sale or dispensing of medicinal products together with councelling for the appropriate and effective use of medicinal products, provision of information to the user on the correct and safe use and preservation of medicinal products, preparation of medicinal products as magistral formulae and officinal formulae and dividing up (A provider of pharmacy services may not be involved in wholesale). At the same time, the added restriction does not prohibit the holder of a license for wholesale trade to repurchase a medicinal product from a pharmacy in order to, e.g., reallocate it (credit or negative sales) or to receive medicinal products from a pharmacy that has discontinued activities subject to § 45 (11) of the Medicinal Products Act – these cases do not represent conventional procurement for wholesale purposes. Furthermore, the Act provides, as an exception, the option to procure medicinal products from a holder of license for pharmacy services upon the import of medicinal products, i.e., in cases of supply from another Member State of the European Economic Area to Estonia, which may be necessary to obtain small amounts of medicinal products (The minimum supply quantities set by manufacturers or wholesale distributors are often higher than needed in Estonia and hence a local wholesale distributor might not be able to obtain a small quantity from a foreign wholesale distributor or manufacturer.).
Advertising medicinal products. In the context of advertising to the general public, the amended Act prohibits offer of any medicinal product or other goods or services free of charge or at a discounted rate together with the purchase of a medicinal product. A similar prohibition was in effect to date; however, the wording did not cover the same medicinal product – it was possible to offer medicinal products with the same name together with the purchase of a particular product, the prohibition applied only to “other” medicinal products. The previous version did not promote rational, strictly need-based use of medicines and called for amendment to avoid ambiguity and support the aim of the regulation.
In the context of advertising to persons qualified to prescribe medicines, the rules for providing promotional samples were changed and instead of the smallest authorised package size as before, samples of the smallest authorised package size actually marketed may now be provided.
The bases for suspending the dispensing and marketing of medicinal products and supervisory competencies were also supplemented.
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