THE NEW EU CLINICAL TRIALS REGULATION

Vitafoods Europe12 May 2016 11:45 – 12:05

Sofie van der Meulenwww.axonlawyers.com

OVERVIEW

• Background and rationale

• Borderline food and medicinal products

• Main changes legal framework for clinical trials under new Regulation

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Background Regulation 536/2014• 17 July 2012: Proposal for a Regulation on clinical trials.

• Regulation: to ensure that Member States base their assessment of an application for authorisation on identical criteria throughout the EU.

• Aims to create an environment that is favourable for conducting clinical trials in the EU with the highest standards for patient safety.

• 16 April 2014: adoption of Regulation

• 28 May 2016: applicable from this date!

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Scope Clinical Trials RegulationArticle 1 CTR:

‘This Regulation applies to all clinical trials conducted in the Union. It does not apply to non-interventional studies.’

The Clinical Trials Regulation applies to investigations in relation to humans intended to:

• Discover or verify effects of one or more medicinal products;• Identify any adverse reactions to one or more medicinal product;• To study absorption, distribution, metabolism and excretion of

one or more medicinal products to ascertain the safety or efficacy.

The CTR applies to medicinal products. Not to nutraceuticals… right? 4

CTR & food products

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Legal definition of nutraceutical =

Stephen L. DeFelice, Founder of the Foundation for Innovation in Medicine, introduced ‘nutraceutical’ in 1989 as a portmanteau of the words ‘nutrition’ and ‘pharmaceutical’. 6

Therefore… nutraceuticals…‘blur the line between food and drugs and it is often difficult — by legal definition — to distinguish between nutrients, food additives, drugs and nutraceuticals.’

Source: Neutraceutical Business Review, www.neutraceuticalbusinessreview.com

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Case law ECJ – Van Bennekom Are vitamin preparations medicinal products?

National authorities should properly assess:

• The function of the product and • the presentation of the product.

In the Van Bennekom case (C-227/82) the ECJ ruled that the form given to the product (pills, capsules) can serve as strong evidence of the intention of the manufacturer to market a medicinal product, but is not conclusive in its own right.

The concept of presentation with respect to borderline products must be broadly conceived. 8

ECJ: Garlic case (C-319/05)

What? Garlic pills marketed as food supplements that were presented in a capsule form.

Are Garlic pills medicinal products?

German authorities: yes.EU Court: No.

• The capsule form is not exclusive to medicinal products. • The supplements did not contain any mention that they aimed to

prevent or treat a certain disease. • Effect of active ingredient allicin was recognized, but did not

transcend the normal metabolism of garlic.

Conclusion: the garlic pills were not considered to be medicinal products, neither by presentation, nor by function. 9

ECJ: Delattre case (C-369/88)

What? Products that were sold in Belgium as food supplements and cosmetics, but qualified as medicinal products in France.

Conclusion EU Court: the products were presented as having positive effects on certain body functions, like the functioning of the gastro intestinal tract or liver and therefore qualified as a medicinal product.

Member States may differ on the qualification of borderline products! The national authorities and courts will have to judge on a case-by-case basis if a product is either a food or a medicinal product.

If a product can be qualified as food and/or cosmetic and as a medicinal product, the product is considered a medicinal product.

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What about Coca Cola? Read more on our blog www.foodhealthlegal.com

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EU Clinical Trials Portal and DatabaseArticle 80 – 82 CTR: “The Agency shall, in collaboration with the Member States and the Commission, set up and maintain a portal at Union level as a single entry point for the submission data and information relating to clinical trials in accordance with this Regulation”.

Why? • To enable cooperation between the competent authorities of the

Member States concerned.• To facilitate communication between sponsors and Member

States (reference to previous submissions).• To enable citizens to have access to clinical information about

medicinal products.

“The EU database shall contain the data and information submitted in accordance with this Regulation”

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EU Clinical Trials Portal and DatabasePublicly accessible unless confidentiality is justified on the following grounds:

• Protecting personal data in accordance with Regulation 45/2001

• Protecting commercially confidential information

• Protecting confidential communication between Member States in relation to preparation of assessment report

• Ensuring effective supervision of the conduct of a clinical trial by Member States

Sponsor has to submit a summary of results and a lay person summary to the Database one 1 year after the end of the trial in the EU.

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Application Part I & Part II (Art. 6 + 7 CTR)

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• Therapeutic & public health benefit aspects

• Risks & inconveniences for the subject

• Manufacturing/importation of IMPs/AMPs

• Labelling• Investigator’s brochure

• Informed consent• Compensation/ rewarding

arrangements• Recruitment arrangements• Data protection rules• Suitability of

- individuals- trial sites

• Damage compensation• Biological samples

Part II – NationalPart I – General One Dossier

EU Portal

Sponsor & Investigator

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Co-sponsorship is possible under Article 72 CTR.

- Either in form of equal responsibility for all sponsors

or

- Contract amongst sponsors which defines responsibilities

The Principal Investigator has to ensure compliance of a clinical trial at a clinical trial site with the requirements of the CTR (Article 73 CTR).

Article 74 (1) CTR: Sponsor has to ensure the establishment of a natural or legal person in the Union as its legal representative.

Article 74 (2) CTR: Member States may choose to accept the establishment of a contact point instead of the establishment of a natural or legal person, if trials are conducted on

- their territory

- or on their territory and the territory of a third country

Safety reporting (Art. 41 & 42 CTR)

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- Investigator: report adverse events/lab abnormalities to sponsor. The protocol may provide that not all adverse events (AE) and serious adverse events are recorded and reported.

- Sponsor: report SUSARs to EudraVigilance (if no resources available, reporting to MS where event occurred, MS to report to EV)

- For IMPs (non-authorised or applied outside terms of marketing authorisation) an annual safety report to be submitted electronically to the Agency

- For authorised IMPs: sponsor to inform the MAH of all SUSARs annually

Informed consent (Art. 28 – 30 CTR)

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Detailed description of information and inclusion of

- Patients in general

- Incapacitated subjects (legal representative, adequate info, involvement in IC process as far as possible, presumed benefit)

- Minors (legal representative, adequate info from trained individuals, involvement in IC process as far as possible, no incentives except compensation, direct benefit or group benefit)

- Subjects in emergency situations (IC can be obtained after inclusion in life threatening or other sudden serious medical conditions, no legal representative available, no earlier expressed refusal to join a CT, no group benefit, minimal risk and burden, approval to be sought asap from legal representative and subject)

Transitory period of 3 years

Until the CTR will become applicable, all clinical trials performed in the European Union are required to be conducted in accordance with the Clinical Trials Directive (2001/20).

The Directive will be repealed as from 28 May 2016, but it will still apply three years from that day to:

• Clinical trials applications submitted before the entry into application (no earlier than 28 May 2016)

• Clinical trials applications submitted within one year after the entry into application if the sponsor opted for the old system

During the transitory period the GCP and GMP Directives (2005/28 and 2003/94) apply to clinical trials authorised under the Clinical Trials Directive. 18

Guidelines

The Commission is working on guidance documents in order to ensure a uniform application of the legislation on clinical trials in Europe.

• Current guidelines are being revised

• Revised and new guidelines are planned to be launched for public consultation in Q3 and Q4 of 2016

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Overview main changes under CTR

• Streamlined application procedure

• Single set of documents for application (Annex I)

• Harmonised procedure for assessment divided in two parts- Part I: joint assessment by all Member States- Part II: each Member State separately

• Simplified reporting procedures

• Increased transparency in trails and outcomes

• Clinical trials outside EU, referred to in an application, have to comply with rules equivalent to EU rules.

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Sofie van der MeulenAxon AdvocatenPiet Heinkade 1831019 HC Amsterdam

+31 88 650 6500+31 6 53 44 05 67sofie.vandermeulen@axonlawyers.com