EMA launches public consultation on accelerated assessment and conditional marketing authorization for medicines with unmet medical need
On 27 July 2015 EMA published its revised guidelines on accelerated assessment and conditional marketing authorization for consultation. The guidelines have been revised to take into account recommendations of the European Commission Expert Group on Safe and Timely Access to Medicines for Patients (STAMP). The revisions are aimed at optimising the use of both these regulatory options and accelerating patients' access to medicines for which there is an unmet medical need. The consultation is open until 31 September 2015. Further information can be found on the EMA website.
Public register for notices on parallel distribution made available
EMA also launched a public register of parallel distribution notices. The register provides information on centrally authorized products that are marketed in the European Union through parallel trade and are considered compliant with the requirements for parallel distribution.
The register can be accessed using the following link.
New lists of harmonised standards for Medical Devices published
New lists with references to harmonized standards for medical devices have been published in the Official Journal of the European Union on 10 July 2015.
The publication can be found on the European Commission website.
General Court clarifies scope of application of Directive 2001/83/EC on Human Medicinal Products
In its judgment of 16 July 2015 the General court clarified the scope of application of Directive 2001/83/EC and the exceptions related to pharmacy preparations (commonly referred to as magistral and officinal formulae).
The clarification had been requested by the Swedish courts in two cases opposing Swedish pharmacies and a Swedish drugs manufacturer (reference for a preliminary ruling in joined cases C-544/13 Abcur AB v Apoteket Farmaci AB and C-545/13 Abcur AB v Apoteket AB and Apoteket Farmaci AB).
Abcur AB is the marketing authorization holder in Sweden for Noradrenalin Abcur since 2009 and Metadon DnE since 2007. Before that time there were no such products on the Swedish market with a marketing authorization. The needs of Swedish patients were met by the defendants with preparations containing the same active substances prepared by Apotek PL (a division and later subsidiary of Apoteket before it became an independent state owned company). They continued to supply patients with these preparations after the authorization of Abcur's products. Abcur started legal proceedings against Apoteket AB and Apoteket Farmaci AB on the basis that the promotion and marketing of such preparations was unlawful and should be ceased.
Article 2 (1) of Directive 2001/83/EC provides that the Directive applies to medicinal products for human use intended to be placed on the market in Member States and either prepared industrially or manufactured by a method involving an industrial process. Taking into account the objective of the protection of public health pursued by EU legislation on medicines, the Court took the view that the concepts of "prepared industrially" and "manufactured by a method involving an industrial process" should be interpreted broadly. According to the Court, an industrial process is characterized in general by a succession of operations which may in particular be mechanical or chemical in order to obtain a significant quantity of a standardized product. As a consequence the standardized production of significant quantities of a medicinal product to be stocked and sold wholesale and the large-scale or serial production of magistral formulae in batches is considered to be industrially prepared or at least to be manufactured by a method involving an industrial process in the sense of Article 2 (1) of the Directive.
Article 3 points 1 and 2 provide exceptions to the general scope of application. Point 1 refers to the magistral formula (which is any medicinal product prepared in a pharmacy in accordance with a medical prescription for an individual patient). Point 2 refers to the officinal formula which is any medicinal product prepared in a pharmacy in accordance with prescriptions of a pharmacopoeia and intended to be supplied directly to patients served by that pharmacy. Being the exception to the general rule, the Court held that these exceptions needed to be interpreted narrowly. As such, the Court clarified that the conditions laid down in point 1 and 2 of Article 3 of Directive 2001/83/EC are cumulative and that the exceptions cannot apply if one of the conditions is not met. In relation to the magistral formula exception, the Court specified that medical prescription must be understood as a prior medical prescription for an identified patient thus excluding production of medicinal products to respond to future demand in abstract. The Court took the same narrow approach for the officinal formula and excluded from the application of this exception any medicinal product prepared by a pharmacy central production unit and supplied to a healthcare establishment. However, for the application of these exceptions, it is irrelevant whether there is another product on the market with the same active substance, same dosage and same pharmaceutical form which has obtained a marketing authorization.
Besides the question on the scope of application of Directive 2001/83/EC, the Court also clarified that medicinal products falling within the scope of Directive 2001/83/EC can also fall within the scope of Directive 2005/29/EC concerning unfair business-to-consumer commercial practices in the internal market provided that the conditions for application of that Directive are met. In case of conflict between the two directives, Directive 2001/83/EC will prevail.
The full text of the judgment can be found on Curia, the website of the European Court of Justice.
The Belgian Pharma 'Pact for the Future': an ambitious plan for innovation to the benefit of patients
On 27 July 2015, the Belgian government and the associations representing pharmaceutical companies from the innovative, generic and biosimilar industries (Pharma.be and Febelgen) concluded a four-year deal, a so-called "Pact for the Future", which is generally considered a 'win-win' for patients, authorities and all actors of the pharmaceutical sector.
This Pact is based on four pillars:
(i) Accelerated access to drugs
New drugs should become available to patients at least two months earlier than is the case today. Such earlier access will be achieved by reducing the time needed to complete drug evaluations and by accelerating the reimbursement process for medicines. For instance, with regard to hepatitis C drugs (for which there is a medical need), a structural reimbursement system will be set up.
The Pact also provides for structural measures aimed at decreasing drug prices. Savings will come from the implementation of a "patent cliff" measure and from price cuts on generic drugs. The "patent cliff" measure is an immediate and steep price decrease as soon as a drug's patent expires, thereby allowing the generic industry to more readily enter into specific markets. The patent cliff measure replaces a former system of gradual price decrease.
(ii) Industry growth and innovation
In consideration of the above savings and to encourage the development of new medicines, the Belgian government agreed to decrease taxes on drug firms' revenues. The Pact also considers implementing additional measures to stimulate further investments in R&D (to facilitate patient recruitment by, e.g., coupling patient data registries). It also clearly shows support in favour of the biotechnology industry by means of fiscal and other measures.
(iii) Greater transparency
In line with the increased transparency obligations resulting from the implementation of the EFPIA Disclosure Code into the Pharma.be Code, the Pact also provides for greater transparency with respect to transfers of value, including within the generic industry, as well as for greater publicity with respect to clinical trials (clinical trials results, whether positive or negative, will have to be made public).
(iv) Budgetary sustainability and predictability
A key objective of the Pact is to offer a more predictable environment and create clarity, including around price reduction policies, thus enabling pharmaceutical companies to better predict their revenues over the next coming years.
The Belgian government wants to pursue a common approach at the European level for drug price reductions, in particular with respect to orphan drugs. In addition, the government has started bilateral consultations with the Netherlands on the price of some medicines.
New Rules on Compassionate Use in Hungary
The Hungarian Parliament amended Act XCV of 2005 on Medicinal Products for Human Use and Amendments of Other Regulations Related to Medicinal Products ("Medicines Act") by adding a new Section 25/C into the Medicines Act that regulates the conditions of the so-called compassionate use of medicines. Section 25/C will enter into force on 1 January 2016.
Hungarian laws regulate certain forms of pre-marketing of medicines (e.g. provisional or special marketing authorization or individual import of a medicine not authorized in Hungary). However, prior to the above amendment of the Medicines Act, compassionate-use within the meaning of Regulation 726/2004/EK was not available in Hungary.
Under the new Section 25/C, it will be possible to use an investigational product or an unlicensed medicinal product (together as "medicinal product"), for the special healthcare interest of patients1, based on the authorization of the National Institute of Pharmacy and Nutrition ("OGYÉI"), if all of the following conditions are met:
- phase II clinical trials were completed or are currently in progress in respect of the medicinal product in a country where the legislation on clinical trials is equivalent to the legislation regulating clinical trials in Hungary or the marketing authorization of the medicine is currently in progress in Hungary or in such country;
- the use of the medicinal product has been requested by the doctor of a patient who is suffering from a life threatening disease or a disease which may cause an irrepairable harm;
- the patient or his/her statutory representative gives his/her written consent based on the information received that shall include the risks of the use of the medicine; and
- the manufacturer of the medicinal product approves the compassionate use and agrees to provide the medicinal product free of charge during the entire duration of the treatment and guarantees the quality of the medicinal product in accordance with good manufacturing practice.
The compassionate use of the medicinal product shall be initiated by the doctor treating the patient by submitting a reasoned request to the OGYÉI that contains the professional reasons for the use of the product and a treatment plan. The doctor will also be responsible for documenting and reporting to the OGYÉI any event arising during the treatment that may affect patient safety.
OGYÉI will decide within 21 days (or in case of urgency, within a maximum 3 days) from the receipt of the request for authorization. The application process will not be subject to any administrative fee. Decisions on compassionate use will be published by the OGYÉI on its official home page.
In order to track the clinical condition of the patient and the efficacy of the medicinal product, OGYÉI will keep records which contain information and data relative to the patient, the doctor treating the patient, the medicinal product and the progress of the treatment.
The Italian Ministry of Health establishes a working group on Mobile Health
On 23 July 2015, the Italian Ministry of Health, General Directorate of medical devices and pharmaceutical services, established a working group on Mobile Health with the task of assessing, for subsequent regulation, the risks deriving from the increasing availability of so called Medical Apps, such as those allowing the collection of clinical data and the transmission of health information to medical staff and patients.
The working group is composed of representatives of the Italian Institute of Health, the Italian Medicines Agency, the Italian Digital Agency, the Ministry of the Economic Development, the Data Protection Authority, Universities and main trade associations (Assobiomedica, Farmindustria and the Italian Society of Telemedicine).
The target of the Ministry of Health is the introduction, within a short period of time, of "regulatory adjustments for Medical Apps with respect to their monitoring, production, distribution and use in the healthcare sector".
The European Court of Justice upholds the legitimacy of the Italian legislation limiting the sale of prescription medicines to pharmacies
By its judgment dated 2 July 2015 the European Court of Justice ("EUCJ") declared inadmissible the request for a ruling submitted by the Regional Administrative Court of Sicily ("TAR") on the compatibility of the Italian legislation limiting the sale of prescription medicines to pharmacies with the provisions of the Treaty on the Functioning of the European Union which prohibit the abuse of a dominant position.
In its decision, the EUCJ clarified that the mere creation of a dominant position through the grant of special or exclusive rights, such as those limiting the sale of medicinal products subject to prescription to pharmacies, is not per se incompatible with the provisions of the EU legislation as, for the purposes of the incompatibility, it is necessary that such exclusive rights led a pharmacy to abuse its dominant position.
Public contracts: unlawfulness of the artificial fractioning of the services to be awarded
By its determination No. 49, dated 10 June 2015, the National Anti-Corruption Authority ("ANAC") confirmed the unlawfulness of the fractioning of work projects aimed at avoiding the application of legislation governing the award of public service contracts.
The determination refers to a procedure for the award of a service contract governed by Legislative Decree No. 163/2006 on public contracts and whose article 125, paragraph 11, allows the direct award of same contract only when the value of the relevant services does not exceed a certain threshold. In the present case, the awarding entity had fractioned the services to be awarded in several segments fixing for each of them a value lower than that established for the application of the public tender procedure.
In this respect, the ANAC stated that, in order to ensure the proper identification of the applicable procedure, the awarding entity must perform a preliminary and unitary assessment of the total value of the services and verify whether such services can be technically referred to the same work. In the affirmative, the ANAC held that the value of the contract must be determined by adding the amounts of all the relevant services and the specific rules set forth for the resulting total amount shall be applied.
Guidelines on the matter of patient dossier
With resolution dated June 4, 2015 the Data Protection Authority approved the "Guidelines on the matter of patient dossier". The Guidelines govern the processing of personal data carried out by healthcare establishments through the patient dossier, an electronic instrument which collects information on the patient's health conditions in order to record his/her medical history with respect to a specific establishment.
The purpose of the Guidelines is to provide a reference framework that will serve as a basis for the data subject to make better choices on the processing of his/her personal data and to align such processing with the principles of legality set forth by the Privacy Code, also ensuring high safety standards.
The basic principle of the Guidelines is that the patient should be allowed to choose, in a fully autonomous way, whether his/her clinical data can be processed in a patient dossier. To this end, the Guidelines establish that the healthcare establishment must provide the patient with all the information concerning the purposes and methods of the processing, the persons that will have access to personal data and the type of operations that can be performed on same, also specifying that the denial of consent is without prejudice to the possibility to access medical care.
Swedish Medical Products Agency proposes new rules
In a recently published investigation report, the Swedish Medical Products Agency (MPA) proposed that pharma companies shall be obliged to report all back orders on medical product to the MPA. In addition, the MPA wish to initiate a coordinated publication of reported back orders as well as a possibility for the authority to issue sanctions on pharma companies not complying with the proposed reporting obligation.
Back order means the drug shortage that occurs when a manufacturer can not deliver a drug to a wholesaler and/or on to pharmacies. This may, among other things, result in the pharmacies not being able to provide the prescribed drug to patients. The situation of back orders has previously been analyzed by the MPA and in 2014 the government instructed the MPA to continue to map the extent of back orders in Sweden. In a recently published investigation report the MPA sets out its findings and analysis as well as suggestions on how to mitigate the risks of back orders.
Every year approximately fifty back orders are reported to the MPA. According to the MPA, there is, however, an underreporting of back ordered medical products which make it difficult for both pharmacies and hospitals to find alternative medical treatments in time.
In Sweden, the Medicinal Products Act provides that marketing authorization holders (MAH) shall report back orders to the MPA. However, in accordance with Swedish industry practice, only so called critical sales stops, i.e. when the back ordered medical product can not be replaced by another medical product, are reported to the MPA. Other, non-critical, back orders are only communicated with pharmacies and/or the healthcare directly.
Changing the current industry practice in Sweden, the MPA in its investigation report now suggests to impose an obligation upon all MAH's to report all temporary and permanent sales stops and back orders, regardless of cause and whether deemed critical or non-critical by the MAH. In addition the MPA suggests that all back orders reported shall be made public by the MPA. In order to maintain the reporting obligation the MPA's also suggests that the reporting obligation imposed shall be accompanied by a possibility for the MPA to issue penalty fines for non-compliance.
Turkey introduces new rules for promoting medicines
Turkey has adopted a new regulation modifying and clarifying rules on promoting medicines for human use and beyond. With limited exceptions, the new regulation entered into force on 3 July 2015.
What the regulation says
- Extended scope
The new regulation extends the promotion rules beyond medicines for human use to include stet nutrition products and medical infant formula.
- Modified rules
The regulation defines several previously undefined terms used in the regulatory framework. These include definitions for pharmaceutical companies' science services, scientific events and product promotion events.
The regulation permits outsourcing promotional activities, resolving a recent debate over whether the outsourcing of promotional activities was indeed permitted. To outsource these activities, the marketing authorization ("MA") holder should submit an executed written agreement with the outsourcing provider to the Turkish Medicine and Medical Devices Authority ("Authority"). Outsourcing does not reduce the MA holder's liability for violating promotion rules.
Unlike the previous regulation, the new regulation prohibits informing healthcare professionals other than physicians, dentists and pharmacists of a product's use and side-effects.
The number of scientific events a healthcare professional can attend in a calendar year with MA holders' sponsorship has been decreased from five to four. A single MA holder is still permitted, however, to sponsor a healthcare professional's attendance at events twice in a calendar year.
As of 1 January 2016, MA holders will be required to notify the Authority of transfers of value exceeding 10% of the gross minimum wage (i.e., over TRY 120.15 for 2015).
The regulation introduces new sanctions for violating promotion rules. Sanctions include a temporary ban from promotional activities, suspension of product promotion personnel licenses, and a temporary ban from sponsoring and participating in scientific and product promotion events.
An important change involves sanctions for repeat violations. Previously, repeat violations — no matter when they occurred — increased sanctions: a warning for the first violation, a three-month ban from promotional activities for a repeat violation, and a one-year ban from promotional activities for further violations, without regard to the amount of time between each violation. With the new regulation, repeating a violation after a one-year lapse will not result in increased sanctions.
- Preserved Promotion Rules
Medicines may still only be promoted to physicians, dentists and pharmacists. This restriction covers non-prescription products, similar to the previous regulation.
Medicines not granted marketing authorization in Turkey cannot be promoted. Off-label promotion is also prohibited. These prohibitions do not apply to promotional activities during international congresses organized in Turkey or conducted at the written request of a healthcare professional.
Healthcare professionals must declare the support they receive from MA holders during their presentations or in their scientific articles.
MA holders' donations to healthcare institutions are permitted under certain limited conditions.
MA holders must notify the Authority of their sponsorships for scientific events and the names of the healthcare professionals they sponsor. Sponsoring scientific events held on beachfront property or in ski resorts during high season is prohibited, except for international scientific events organized in a different country every year.
Strict limitations on promotional materials and free samples are preserved, with slight modification.
Product promotion personnel must be trained and accredited by the Authority.
Actions to consider
Companies selling or promoting enteral nutrition products and medical infant formula must take immediate action to comply with the new regulation. We recommend introducing policies on interactions with healthcare professionals and promotional activities, as well as training sales and marketing teams.
Pharmaceutical companies may now consider outsourcing their promotion activities. Since outsourcing does not remove the MA holder's liability, outsourcing contracts must be well-drafted to ensure recourse mechanisms and legal safety for the outsourcing company.
Pharmaceutical companies should also develop compliance rules and notification mechanisms to comply with the new requirements concerning transfers of value.
We recommend that pharmaceutical companies undertake a full revision of internal policies on interactions with healthcare professionals and promotional activities.
Turkey revises medicine pricing rules
A new decision, On the Pricing of Medicines for Human Use, published on 10 July 2015, has revoked the controversial 2007 pricing decision and has introduced a reference price for pharmaceuticals of 70% of the previous year's average EUR/TRY exchange rate.
Prior to the publication of the new pricing decision, a 2007 Council of Ministers decision established the general framework for Turkish medicine pricing rules. Further detail of the pricing rules was set out in the Ministry of Health Communiqué, On the Pricing of Medicines for Human Use.
Turkey uses a reference pricing system. The "reference price" for a medicine is the lowest of the sale-to-warehouse prices in (i) the five EU reference countries, (ii) the country where the product is manufactured, and (iii) the country from which the product is imported, provided the product has received marketing authorization and is actually sold in these countries. Discounts are not considered.
Under the 2007 pricing decision, reference prices were determined in Euro, and then converted into Turkish lira at a fixed exchange rate. The 2007 decision required the Medicine Price Evaluation Commission ("Pricing Commission") to convene quarterly and, as needed, extraordinarily, to revise the exchange rate in line with exchange rate fluctuations. On 2 April 2009, the Pricing Commission fixed the EUR/TRY exchange rate at 1.9595. Since then, however, the Pricing Commission failed to convene and revise the exchange rate, even though the lira devalued substantially against the Euro, putting severe pressure on pharmaceutical companies with regard to pricing medicines.
In response, the Research-Based Pharmaceutical Companies Association (Tr. Araştırmacı İlaç Firmaları Derneği or "AIFD"), a Turkish pharmaceutical industry association, sued the Ministry for the Pricing Commission's failure to revise the exchange rate. The court ruled in AIFD's favor, ordering the Pricing Commission to convene. Following this ruling, the Pricing Commission convened but did not revise the exchange rate, prompting AIFD to bring another action against the Pricing Commission for failure to adjust the exchange rate. The court again ruled in AIFD's favor and annulled the Pricing Commission's decision not to revise the exchange rate.
What the new decision says
The new pricing decision's most significant provision, Article 2(2), states the reference price is now 70% of the previous year's average EUR/TRY exchange rate. Rules on reference countries, maximum sale-to-warehouse prices, and warehouse and pharmacy profit margins remained generally the same, with only slight numerical changes. The Turkish government revised the pricing rules to set a 70% coefficient for the EUR/TRY exchange rate to avoid implementing the previous pricing rules which did not include a coefficient.
The new pricing decision is effective immediately. As a transitional matter, under Provisional Article 1, the Pricing Commission is to publish the average EUR/TRY exchange rate for the last 90 days (rather than the previous year) by 21 July 2015, which will be the basis for reference prices until January 2016.
Implications for pharmaceutical companies
Pharmaceutical companies must revise their product prices in line with the new pricing rules.
UK Court of Appeal interpretation of Numerical Ranges in Patent Claims
In Smith & Nephew plc v ConvaTec Technologies Inc1 the Court of Appeal overturned a High Court decision, holding that ConvaTec's process patent claim for a silverised wound dressing, which specified the presence of a binding agent “in a concentration between 1% and 25%”, was infringed by Smith & Nephew’s modified process in which the agent was present in a concentration of 0.77%.
ConvaTec is the proprietor of Aquacel, a wound dressing product. ConvaTec's EP(UK)1343510 ("Patent") covers a three-step process for making antimicrobial materials used in wound dressings. The third step of its method involves the use of a binding agent in a concentration of “between 1% and 25%”. Smith & Nephew manufactured its own wound dressing in accordance with this method save that it used a concentration of binding agent of 0.77%. In January 2013 Smith & Nephew commenced action for a declaration of non-infringement of the Patent. ConvaTec counterclaimed alleging infringement.
The High Court decision
The High Court held that Smith & Nephew’s process did not infringe the Patent. The Judge held that the skilled person would adopt the 'significant figures approach' to the construction of the words “between 1% and 25%”. This saw 1% expressed to an accuracy of one significant figure and 25% to an accuracy of two significant figures. Since the lowest number that rounds (to one significant figure) to 1% is 0.95% and the highest number that rounds (to two significant figures) to 25% is any number < 25.5%, the claim encompassed all concentrations ≥ 0.95% and < 25.5%.
The Court of Appeal decision
The Court of Appeal began by setting out the general approach to the interpretation of a patent claim as per Kirin Amgen2: the question is always what a skilled person would have understood the patentee to mean. The Court of Appeal elaborated by noting that "the patentee is likely to have chosen the words… with the benefit of skilled advice and, in so far as he has cast his claim in specific rather than general terms, is likely to have done so deliberately."
A literal interpretation of the claim (where the limits of would be exactly 1% and 25%) was swiftly rejected by the Court of Appeal on the basis "that the patentee intended the limits to be understood in a less precise way".
The Court of Appeal then considered whether the skilled person would understand the numbers to be expressed in terms of whole numbers (or zero decimal places) or significant figures.
Disagreeing with the High Court’s construction, the Court of Appeal held that there is "no logical basis for preferring the significant numbers approach". The High Court erred in that it placed too much emphasis on the fact that many of the ranges in the specification are defined by limits that are not whole numbers. Additionally, application of the significant figures approach led to asymmetrical distribution (a range 0.05 below the lower numerical limit but up to 0.5 above the upper numerical limit) because of the anomaly when rounding to the number 1 using the significant figures approach. This anomaly was incorrectly disregarded by the High Court. Additionally, the Court of Appeal noted that the Patent specification made it clear that there was not technical reason for the 1% - 25% limit (a wider range would also work) and so there was no reason to interpret the range in precise terms.
Ultimately, the Court of Appeal held the skilled person "would understand the 1% and 25% limits to have been expressed to the nearest whole number". Consequently, the claim covers all concentrations of binding agent ≥ 0.5% and < 25.5%, meaning Smith & Nephew's process infringed.
This decision underlines the reluctance of the Courts to apply interpretations to numerical ranges where the skilled reader would have no reason to suppose the patentee intended the numerical range to be understood in such a way. While these principles are important to those who are keen to avoid infringing another’s patent, patentees should also be mindful of prescribing limits in precise terms when drafting patent claims, such that they may inadvertently narrow the scope of protection.