European Commission consultation on providing information to patients

Electronic-only applications for marketing authorisation 

Best practice guidance on joint working between the NHS and the Pharmaceutical Industry

Ethical considerations for clinical trials in children

The European Commission sector inquiry into Pharmaceuticals: a shot in the arm for generics?

On 16 January 2007 the European Commission launched a "sector inquiry" into the EU pharmaceutical market by conducting dawn raids at the European premises of major suppliers of branded and generic drugs.

Sector inquiries - detailed and broad-ranging investigations based on a suspicion that a market should be more competitive - have become a favoured tool of the Commission in recent times.  But this inquiry immediately set itself apart from the others because it was begun with dawn raids - dramatic powers usually reserved for investigating dishonest price-fixing and other cardinal competition sins.

The Commission explained that the element of surprise was crucial because, in contrast to other sector inquiries, there was a risk that confidential documents might be concealed or destroyed.

Why conduct a sectoral inquiry?

The Commission is concerned that the number of medicines being launched has declined in recent years.   It is also suspicious of the fact that manufacturers of generics do not always move into new markets, which emerge when a patent expires, as promptly as they might. 

The sector inquiry is an information-gathering process to assess whether these concerns are justified and, if so, whether they are the result of an impaired competitive process.  It does not presuppose any infringement of competition law by an individual company - hence the market-wide focus. However, investigations into individual companies under EC competition law, which prohibits restrictive practices and abuse of dominance, may well follow.

A change of Commission focus?

Pharmaceutical companies are not unfamiliar with competition law.  However, previous Commission activities have focussed on practices which impeded parallel trade and thus offended the EC commitment to a single European market.

The sector inquiry is interesting because it seems that the Commission has generics and the use/misuse of IP rights in its sights.  More specifically, the Commission intends to focus on whether settlement agreements (struck in the context of patent disputes) infringe competition law.  The Commission will no doubt scrutinise practices involving the delayed launch of a generic in return for payments from the patent holder to the infringer.

This is unchartered territory for the Commission. While US courts have had to consider the antitrust implications of settlement agreements (with varying outcomes) the Commission has never had to decide on their compatibility with EC competition law.

The Commission will also examine whether companies have created artificial barriers to market entry - for example through the misuse of patent rights, vexatious litigation or any other means which might amount to an abuse of dominance. 

The reference to "vexatious litigation" - the notion that patent holders are relying on sharp practice and deep pockets to dissuade the prompt entry of generics - is intriguing.  Drawing a distinction between unwarranted litigation and the justified exploitation of IP rights is likely to be difficult.

It comes as less of a surprise that the Commission is tackling the misuse of patent rights.  Recent Commission practice shows that the abuse of patent rights by dominant pharmaceutical companies is a priority:

-- In 2005, the Commission fined AstraZeneca €60 million for having abused a position of dominance in ulcer drugs by (i) giving national patent offices incorrect dates for calculating the length of protection in relation to the ulcer drug Losec; and (ii) withdrawing authorisations for the capsule form of Losec in some markets - apparently to delay the entry of generics. 

-- In February 2007, the Commission began proceedings against Boehringer for allegedly  misusing the patent system in order to exclude competition in respect of chronic obstructive pulmonary disease drugs.

Outside the pharmaceutical sector, the Commission has also pursued dominant companies for patent abuse.  In August 2007, it alleged that Rambus had engaged in a "patent ambush" - deceptive conduct in the context of a standard-setting process for computer chips which involved not disclosing the existence of the patents which it later claimed were relevant to the adopted standard. 

Next steps

The Commission will now send information requests to companies active in the sector - in addition to those already raided.  It aims to publish an interim report towards the end of 2008, and then adopt a final report in spring 2009.

A range of outcomes is possible - from taking follow-on enforcement action against specific companies (as occurred after the Commission's sector inquiry into the energy sector); recommending legislative reform or encouraging companies to address issues themselves by adopting codes of conduct.

Conclusions and implications

The Commission has shifted its attention from the parallel trade of drugs to the importance of generics versus brands - and the extent to which IP rights are being used to blunt their competitive impact.  In particular, the Commission seems interested in the type of behaviour engaged in when a patent is near the end of its lifetime. 

The sector inquiry is therefore a reminder of the inherent tension between IP rights, which confer a monopoly in order to ensure innovation, and competition law which is opposed to artificial barriers to market entry.  Defining the boundary between the legitimate defence of IP rights and anti-competitive conduct will not be easy.

Inevitably, policy factors will play a significant part in the Commission's thought process.  National governments - as major purchasers of drugs - will be keen to be heard and pharmaceutical companies will need to make coherent and persuasive submissions, for example, in order to justify the terms of settlement agreements they will need to show that threats of litigation were underpinned by sound rational legal bases. 

There is a real risk of follow-up action, namely, possible investigations into the conduct of individual companies under EC competition law.  If so, the Commission can be expected to take a tough stance.  In the meantime, companies will need to keep under careful review their patenting and litigation strategies. 

For further information on this article, please contact Grant Murray or Keith Jones of the London office.

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European Commission consultation on providing information to patients

The European Commission has launched a public consultation on a new proposal to ensure that information given to patients on prescription-only medicines reaches the highest standards.  The proposal follows a provision in Directive 2004/27/EC that the Commission should present a report to the European Parliament and Council on current practice across member states.  This report was published on 20th December 2007  and concluded that rules and practices on information provision vary widely across the EU, leaving inequality between member states.  It expressed concerns that patients and the public were not always able to discover sufficiently detailed and reliable information on the prescription medicines available to them. 

In response to these concerns, the current consultation has been initiated, giving stakeholders and all interested parties in the EU who deal with medicinal products an opportunity to contribute to forming a new regulatory framework.  The new directive, following the consultation, will establish a set of rules to which authorised marketers of medicines will be subject.  In keeping with past policy, the Commission emphasises, though, that healthcare professionals should remain the primary source of all information in this area. 

The proposed legislation has a number of simple policy objectives aimed at safeguarding the interests of patients.  The framework will be designed to ensure that patients across the EU have access to clear, objective and reliable information which is not unduly influenced by any commercial interest or pressures.  To this end, the present ban on advertising direct to the consumer regarding prescription medicines will be maintained and efforts will be made to avoid excessive bureaucracy.

As a practical step to establish a level playing field for the public across member states, the new rules on information provision will be harmonised so that a clear distinction is universally presented between material which advertises a product and material which informs the consumer.  There will be minimum standards applied to the factual information which must be given with any medicinal product, while maintaining the current distinct treatment of prescription and over-the counter medicines.  Strict rules governing information on prescription medicines will be revised and maintained.  Such information should neither contradict nor go further than the approved summaries of product characteristics.      

Whilst maintaining the ban on advertising prescription products, the dissemination via the media of information on such products will continue, monitored by national regulatory bodies established for the purpose and overseen by an EU-wide Advisory Committee.  Information actively sought by consumers will also be monitored by national bodies.  This would include internet sites containing product information, which could also be used to monitor any consumer complaints to pharmaceutical companies. 

Crucially, the new regulations will establish quality criteria for all relevant information, ensuring patient access to unbiased objectivity, reliability and clarity in the information they receive.  It will not be permitted to draw comparisons between products and all statements must be evidence-based, protecting consumers from any misleading claims.  

A copy of the consultation can be obtained from the Commission website.

For further information on this article, please contact Sam Parr or Paul Hawkins of the London office.

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Processing of personal data in clinical trials

By resolution No. 62 of 29 November 2007 (the "Resolution"), the Italian Data Protection Authority ("IDPA") issued guidelines for the legitimate processing of personal data in clinical trials.

As a result of a number of investigations and enquiries into data processing practices by pharmaceutical companies, the IDPA identified that clinical trials carried out by hospitals or public research centres are normally promoted by a pharmaceutical company acting as sponsor.  Personal data of patients participating in a clinical trial are collected and processed by a hospital's physicians, but some of this data, including clinical/medical information, is made available to the sponsor, its employees and/or to third party providers engaged by the sponsor (e.g., clinical study monitors), to enable such parties to monitor the development of the clinical trial and examine possible adverse reactions.

The IDPA also identified that, in most cases, a sponsor is of the view that it is not bound by the requirements set out in Italian privacy laws on the basis that it does not process patient identification data because the hospital's physicians provide the sponsor with data on the basis of alphanumeric codes, which do not enable patient identification.

The IDPA does not share this point of view and, by the above Resolution, stated the following:

1. Even though a hospital's physicians use unique alphanumeric codes to identify the patients subject to a clinical trial, such measure does not ensure the actual anonymization of patient identification data.  Codification of patient data does not prevent a sponsor from ultimately knowing the patient's identity, given that, in practice, the parties monitoring a clinical study are allowed access to the patient's clinical records and considering also that a sponsor is, generally, provided with demographic information on the patients.  On such grounds, patient identification alphanumeric codes communicated to a sponsor must be considered sensitive data of the patients.

2. Based on the above, both a hospital and a sponsor process sensitive data of patients and, since they have different and separate responsibilities with respect to the data processing activities involved in clinical trials, they both must be considered as "Data Controllers". As a consequence, both the hospital and the sponsor must meet the requirements set out in Italian laws on privacy and data security.

3. Accordingly, patients must be provided with comprehensive privacy information clarifying that their personal and sensitive data will be processed by both the hospital and the sponsor and specifying the purposes of their data processing and the scope of communication/transfer of this data.

4. Based on the above privacy information, patients should consent in writing to the processing of their data by a sponsor, its employees or third party providers.

5. A Sponsor, as Data Controller, must adequately instruct (in writing) all its employees and external third party providers (e.g., the clinical study monitors) that may access patient data.  All such parties must be appointed either as Data Processors or designated as persons in charge of processing.

6. Patient data must be kept for the maximum time permitted by the laws regulating a clinical trial or for a longer time agreed between the hospital and the sponsor. A longer retention period must be authorised by the IDPA.

7. Both the hospital and the sponsor must adopt security measures that are more stringent than standard measures.

The IDPA will soon establish a deadline for implementation of the obligations set out by the Resolution.

For further information on this article please contact Serena Grosso or Roberto Cursano of the Rome office.

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Royal Decree 1344/2007 on pharmacovigilance

Royal Decree 1344/2007 (the "Royal Decree") develops chapter VI of Title II of the Law 29/2006, dated 29 July 2006 on use of medicinal products and medical devices (sections 53 to 57).  It regulates monitoring of the risk/benefit balance of medicinal products for human use. Its scope does not extend to pharmacovigilance for veterinary use (section 57).

The Royal Decree also establishes a general requirement that electronic notification should be made of any adverse reactions to medicinal products. This is an obligation for all Spanish pharmacovigilance agents.  Furthermore it emphasizes the importance of post authorisation studies that contribute to identification and minimisation of risks.

New definitions

New definitions contained in the Royal Decree are the result of international harmonisation.  Some examples follow:

1. Risks associated with the use of medicinal products: Any risk relating to the quality, safety or efficacy of a medicinal product as regards patient health or public health; any risk of undesirable effects on the environment.

2. Risk-benefit balance: An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks.

3. Risk management plan: A document that plans pharmacovigilance activities with the purpose of identifying safety issues.

4. Medication errors: Failure by action or inaction in the treatment process that can cause damage to patients.

Duties of health professionals

The Royal Decree establishes a duty to notify serious adverse or unexpected reactions arising from use of medicinal products.  Suspected adverse reactions that are a consequence of a medication error should also be notified in accordance with special procedures contained in "Good practices of pharmacovigilance in the Spanish system of pharmacovigilance of medicinal products for human use".

Duties of marketing authorisation holders

Marketing authorisation holders of homeopathic medicinal products are obliged to make periodic safety update reports.   Marketing authorisation holders are also required to record and report all suspected serious adverse reactions associated with an authorised medicinal product or medicinal products that have been imported to Spain. Such notifications are made electronically to the Spanish Pharmacovigilance data processing network.

A marketing authorisation holder may also be obliged to make a report on the risk/benefit balance of a medicinal product if required by the Spanish Agency.  The holder of a marketing authorisation may not communicate information relating to pharmacovigilance concerns to the general public without giving prior or simultaneous notification to the Spanish Medicinal Products and Medical Devices Agency.

Urgent modifications

A new section creates the possibility of making an urgent and provisional change to a medicinal product information datasheet if a new risk to public health is discovered.  The urgent modification of a marketing authorisation may also be considered for safety reasons.

Post-authorisation studies

In addition to provisions in previous regulations, the Royal Decree creates a Coordination Committee for Post-Authorisation Studies, formed by representatives of the Autonomous Communities and the Spanish Medicinal Products and Medical Devices Agency. This Committee is in charge of establishing the conditions for observational post-authorisation studies.

Requirements for post-authorisation studies can arise when (i) it is a condition of the authorisation of a medicinal product, (ii) when an authority requires it or (iii) when it is part of a risk management plan.  Sponsors of post-authorisation studies are obliged to follow applicable European security guidelines.

For further information on this article, please contact Cecilia Pastor or Ester Navas of the Madrid office.

New consortium to run National Clinical Audit

A new consortium has been appointed to run the National Clinical Audit and Patient's Outcomes Programme ("NCAPOP").  The consortium is comprised of the Academy of Medical Royal Colleges, the Royal College of Nursing and the Long Term Conditions Alliance and will be known as the Healthcare Quality Improvement Partnership.  The clinical audit programme was managed previously by the Healthcare Commission.

The new programme will commence on 1 April 2008, following a transition period that started in January 2008.  The new consortium will also have a role in supporting the National Clinical Audit Advisory Group that provides advice and guidance on matters relating to clinical audit, including proposals for new audits.

An additional £3.2 million per year has been allocated to the NCAPOP to expand its function to provide wider support activities in addition to its existing function of commissioning audits. 

For further information on this article please contract Paul Hawkins or Beatriz Araujo of the London office.

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Electronic-only applications for marketing authorisation

The European Medicines Agency ("EMEA") has announced plans to implement the electronic-only submission of information in support of marketing authorisation applications using the centralised procedure.  This announcement is part of the EMEA's strategy for implementation of the Electronic Common Technical Document ("eCTD") as the required format for electronic submissions.

From 1 July 2008, the EMEA will accept electronic-only submissions without requiring additional documents to be submitted in paper copy.  This will apply to all new applications and all other types of submissions, e.g. variations or renewals.  Electronic-only submissions will be strongly recommended by the EMEA from 1 January 2009.  At this time, paper will be an exception to the recommended format.  From 1 July 2009, the EMEA will strongly recommend electronic-only submissions using the eCTD format.

The EMEA has issued a question-and-answer document relating to these changes, which is available from the EMEA website.

For further information of this article, please contact Paul Hawkins or Beatriz Araujo of the London office.

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Best practice guidance on joint working between the NHS and the Pharmaceutical Industry

The Department of Health ("DoH") has published new guidance on joint working between the National Health Service ("NHS") and the pharmaceutical industry.  The guidance provides advice as to how, for example, Primary Care Trusts, pharmaceutical companies and clinicians can work together to identify particular medical needs in the community.  It aims to:

• encourage NHS organisations and staff to work together to deliver high-quality healthcare; and

• inform and advise NHS staff of their main responsibilities when considering entering into joint working arrangements with the pharmaceutical industry.

A toolkit on joint working between the NHS and pharmaceutical industry, focusing on learning from useful examples with a view to recommending and sharing best practice, is due to be issued to augment this guidance in March 2008.  The toolkit is currently under development and is being piloted with a number of NHS organisations.

A copy of the guidance can be obtained from the DoH website.

For further information on this article please contact Nicola Mead or Paul Hawkins of the London office.

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Ethical considerations for clinical trials in children

An ad hoc group chaired by the European Commission has published a paper on ethical considerations for clinical trials in the paediatric population.  The paper contains the group's recommendations for the development of guidelines for Directive 2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human use.  It focuses specifically on various ethical aspects of clinical trials performed in children from birth to the legal age of adulthood.   It is hoped that, as the approval of clinical trials, including ethical approval, is performed by the Member States, any recommendations on ethical aspects of clinical trials in children will also facilitate a harmonised approach to the application of clinical trials in the EU and in whichever country the paediatric trial occurs.

The paper discusses the special considerations for children in clinical trials.  Protection against the risks of research in such a vulnerable population is considered paramount while the group emphasise that this should not deny children the benefits of research.  In general, children are not legally able to consent to their participation in trials.  This lack of legal ability to consent has implications on the design, parameters and on-going monitoring and analysis in conducting the trials.

A copy of the recommendations can be obtained from the European Commission website.

For further information on this article please contact Nicola Mead or Paul Hawkins of the London office.

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