Regulation (EC) No 45/2001 regulates the protection of individuals with regard to the processing of personal data by Community institutions and bodies.
Especially an improvement for multicenter trials covering various jurisdictions.
Vitafoods eu clinical trials regulation
THE NEW EU CLINICAL
12 May 2016 11:45 – 12:05
Sofie van der Meulen
• Background and rationale
• Borderline food and medicinal products
• Main changes legal framework for clinical trials under new
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
• 16 April 2014: adoption of Regulation
• 28 May 2016: applicable from this date!
Scope Clinical Trials Regulation
Article 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
The CTR applies to medicinal products. Not to nutraceuticals… right?
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
‘blur the line between food and drugs and it is often difficult — by legal
definition — to distinguish between nutrients, food additives, drugs and
Source: Neutraceutical Business Review, www.neutraceuticalbusinessreview.com
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
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
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
If a product can be qualified as food and/or cosmetic and as a
medicinal product, the product is considered a medicinal
What about Coca Cola?
Read more on our blog
EU Clinical Trials Portal and Database
Article 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”.
• 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
“The EU database shall contain the data and information submitted
in accordance with this Regulation”
EU Clinical Trials Portal and Database
Publicly accessible unless confidentiality is justified on the
• 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
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
Application Part I & Part II
(Art. 6 + 7 CTR)
• Therapeutic & public
health benefit aspects
• Risks & inconveniences
for the subject
on of IMPs/AMPs
• Investigator’s brochure
• Informed consent
• Compensation/ rewarding
• Recruitment arrangements
• Data protection rules
• Suitability of
- trial sites
• Damage compensation
• Biological samples
Part II – NationalPart I – General
Sponsor & Investigator
Co-sponsorship is possible under Article 72 CTR.
- Either in form of equal responsibility for all sponsors
- 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
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)
- 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
- For authorised IMPs: sponsor to inform the MAH of all SUSARs annually
(Art. 28 – 30 CTR)
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
The Commission is working on guidance documents in order to
ensure a uniform application of the legislation on clinical trials in
• Current guidelines are being revised
• Revised and new guidelines are planned to be launched for
public consultation in Q3 and Q4 of 2016
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.
Sofie van der Meulen
Piet Heinkade 183
1019 HC Amsterdam
+31 88 650 6500
+31 6 53 44 05 67