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Seltene Helden?
Orphan Drugs und Seltene Erkrankungen in Deutschland
10. IGES Innovationskongress
Europäische Gesetzgebung und Trends
18. Oktober 2013, Berlin
Dr. Alexander Natz
A. Allgemeiner Überblick: Aktuelle Gesetzgebungsverfahren
B. Der Schutz von “Commercially Confidential Information”
C. Bindungswirkung der Ausweisung als “Orphan Medicinal Product”
Übersicht
A. Allgemeiner Überblick: Aktuelle Gesetzgebungsverfahren
New legislation / delegated acts / impelmentation: • Transparency Directive (Amended COM proposal 20.03.2013)
• Clinical Trials Regulation (COM proposal 17.07.2012)
• Medical Devices / IVD regulations (COM proposals 26.09.2012)
• Horizon 2020 / Funding (COM proposal 30.11.2011)
• API Importation from third countries into the EU (deadline 02.07.2013)
• Delegated acts Unique Identifier (Falsified Med. Directive) (likely in 2014)
• Delegated / Implementing Acts und Fees Pharmacovigilance (02.07.2012)
• EU GDP Guideline (released 07.03.2013 / applicable 08.09.2013)
• Plus: Access to MA and CT Data via EMA/NCA/CT database; recast
Directive 2001/82/EC, EMA Fee Regulation, Variations Reg. (EC) 1234/2008
EU Regulations / Directives / Guidelines / Implementation 2013 - 2016
Intended changes by COM proposal:
• Transfer of ECJ case law (demand-side-related measures) – positive
• No mandatory EU list of national prices – welcomed
• HTA-procedures in scope of Directive – positive
• Results of MA (Q/S/E) shall not be questioned in P&R decision – welcomed
• Time limits for P&R decisions - positive
• Managed entry agreements remain confidential – welcomed
• Public procurement law (not Transp. Directive) governs tenders – positive
• No specific provision on personalized/stratified medicine – negative;
• No inclusion of medical devices – negative.
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Transparency Directive: EUCOPE Position
Transparency Directive: Orphan designation - no re-assessment at
national level
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Article 13(1) COM 2013 168
Additional proof of quality, safety, efficacy or bioequivalence
In the framework of pricing and reimbursement decisions, Member States shall
not re-assess the quality, safety, efficacy, bioequivalence or biosimiliarity of the
medicinal product or the criteria for orphan designation which have already
been assessed during the marketing authorisation procedure.
EUCOPE Position: This is welcomed;
However for consistency with other amendments to this article, it might be useful
to amend Article 2 (Definitions) to include the definition of orphan medicinal
products, as well as the definition of the criteria for orphan designation.
Transparency Directive: Proposed measures related to price transparency
• The Commission proposal did not establish the set up of a database for national
prices;
• However, MEPs tabled an amendment requesting more price transparency,
stating that competent authorities shall publish in an appropriate publication (…)
a complete list of medicinal products covered by their health insurance
systems, the prices of which have been fixed (…) with the prices which may
be charged for such products.
• In the course of the discussions, this request has been partly included in Recital
15a stating that the Commission and the Member States should (also) examine
how to continue to co-operate on the functioning of the EURIPID price
information database, which provides EU wide added value in terms of price
transparency.
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Transparency Directive: Commission statement on plans to set up a
price database
Industry Commissioner Tajani on 10 December 2012 on Parliamentary Question E-
009635/2012 from 22 October 2012:
“Setting up or maintaining a medicine price database falls outside the EU
competences (Article 168(7) TFEU) since it touches upon the substance of the
decisions regarding pricing of medicinal products and their inclusion in the scope of
health insurance systems“
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EUCOPE: the mid-sized companies perspective
EUCOPE represents
• 900+ mid-sized companies via the associations EMIG, BPI, BioDeutschland, SwedenBio, IML, PEF
• Board represents, inter alia, companies from Sweden, UK, Bulgaria, Italy, Greece, Germany, the Netherlands
• Companies represented, inter alia, B. Braun, SigmaTau, Ferring, Grifols, Norgine, Biogen Idec, Celgene, Alexion, InterMune, Biotest, BioMarin…
• Recognized stakeholder by EMA, European Commission and the European Parliament.
EUCOPE Positions
• http://www.eucope.org/en/positions/
EUCOPE general objectives (see: www.eucope.org)
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B. Der Schutz von “Commercially Confidential
Information”
Der Schutz von “Commercially Confidential Information”
I. Aktuelle Gesetzgebungsverfahren:
Vorschlag KOM VO Klinische Studien
Vorschlag KOM VO Medizinprodukte
II. Geplante EMA Verwaltungspraxis: Proaktive Veröffentlichung von
Studiendaten
III. Anhängige Gerichtsverfahren im Hinblick auf derzeitige
Rechtslage: VO 1049/2001 (InterMune / AbbVie Fälle)
IV. Selbstverpflichtung der Industrie (PhRMA-EFPIA Prinzipien)
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Commission Proposal for a Clinical Trials Regulation
Commission Proposal (emphases added):
Article 78 - EU database
1. The Commission shall set up and maintain a database at Union level (hereinafter,
the ‘EU database’). The Commission shall be considered controller of the database.
The EU database shall contain the data and information submitted in accordance
with this Regulation.
(…)
3. The EU database shall be publicly accessible unless, for all or parts of the data
and information contained therein, confidentiality is justified on any of the
following grounds:
– protecting personal data in accordance with Regulation (EC) No 45/2001;
– protecting commercially confidential information;
– ensuring effective supervision of the conduct of a clinical trial by Member States.
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Commission Proposal for a Clinical Trials Regulation
Tabled Amendments by MEPs (emphases added):
1. Recital 20a:
• “[…]For the purposes of this Regulation, in general the data included in
clinical study reports should not be considered commercially confidential
once a marketing authorisation has been granted or the decision-making
process on an application for marketing.”
2. Recital 25a (new)/Article 34(3)(1)/Annex IIIa
• The sponsor shall submit the full clinical study report within 30 days after
marketing authorisation has been granted or if the sponsor has decided not to
submit an application for marketing authorisation. Annex IIIa enlists the elements
of the “summary of the results of the clinical trial”, which includes, inter alia,
• “7. The protocol and its subsequent modifications.”
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Comission Proposal for a Medical Devices Regulation
Article 53 - Electronic system on clinical investigations (emphases added)
1. The Commission shall (…) set up and manage an electronic system to create
the single identification numbers for clinical investigations referred to in Article 51(1)
and to collate and process the following information:
(a) the registration of clinical investigations in accordance with Article 52;
(b) the exchange of information between the Member States and between them and
the Commission in accordance with Article 56;
(c) the information related to clinical investigations conducted in more than one
Member State in case of a single application in accordance with Article 58;
(d) reports on serious adverse events and device deficiencies referred to in Article
59(2) in case of a single application in accordance with Article 58.
(…)
3. The Commission shall be empowered to adopt delegated acts in accordance with
Article 89 determining which other information regarding clinical investigations
collated and processed in the electronic system shall be publicly accessible to
allow interoperability with the EU database for clinical trials on medicinal products for
human use set up by Regulation (EU) No […/…]. Article 52(3) and (4) shall apply.
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Commission Proposal for a Medical Devices Regulation
Tabled Amendments by MEPs (emphases added):
(…) The Commission shall also ensure that healthcare professionals have
access to the electronic system. The information referred to in points (d)
and (da) of Article 53 shall be accessible to the public in accordance
with Article 52(3) and (4).
2a. Upon a reasoned request, all information on a specific medical
device available in the electronic system shall be made accessible to
the party requesting it, save where the confidentiality of all or parts of the
information is justified in accordance with Article 52(3).
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EMA Draft Policy “Publication and access to clinical-trial Data”
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EMA Draft Policy Paper for Public Consultation “Publication and
access to clinical-trial Data” – Status Quo
• Currently disclosure of data only after request of third party
according to the provisions of Regulation 1049/2001
• In the future EMA intends to proactively disclose data to the public:
the draft policy includes three different levels of access, together with
corresponding conditions for publication and use, depending on the type
of data involved
• Draft policy published on 24 June 2013
• Stakeholders had until 30 September 2013 to submit their comments on
the Agency’s proposals
• The new policy shall (officially) enter into force as of 1 January 2014
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EMA Draft Policy Paper for Public Consultation “Publication and
access to clinical-trial Data” – EUCOPE Concerns
1. Definition of CCI
“For the purpose of the policy, CCI shall mean any information that is not in the public
domain or publicly available and where disclosure may undermine the legitimate
economic interest of the owner of the information. CCI falls broadly into two
categories: trade secrets (including formulas, programs, process or information
contained or embodied in a product, etc.) and commercial confidences.”
2. Scope of CCI identified by EMA so far
“CT data/documents containing CCI: a small number of CT data/documents can
contain CCI. This applies to information such as details of the investigational
medicinal product itself, some in vitro studies, or bioanalytical data characterising the
product (points 2.7.1, 5.3.1 and 5.3.2 of Annex I).”
3. Lack of Protection of CCI
“The Agency respects and will not divulge commercially confidential data or
information. In general, however, CT data cannot be considered CCI; the interests of
the public health outweigh considerations of CCI.”
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Pending Court Cases – Intermune/EMA & AbbVie/EMA - Overview
• InterMune and AbbVie challenged decisions of the EMA to disclose to
third parties, under EU public access to documents rules (Regulation
1049/2001), detailed pre-clinical, quality and clinical data
(InterMune) contained in the dossier supporting its successful
application for an EU marketing authorisation for their products.
• Decision on interim measures taken by the General Court on 25 April
2013, granting InterMune’s and AbbVie’s application for an interim
injunction preventing the EMA from releasing the contested
information pending the Court’s decision on the substantive
issues.
• EMA filed an appeal with the Court on July 5 which was heard on 14
October 2013.
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Pending Court Case – InterMune vs EMA – General Court’s view in the
decision on the interim measures, T-73/13 I
Rn 45: "... The EMA failed to make a detailed assessment of the
arguments and evidence submitted by the applicants about the
confidential nature of the information at issue before adopting the contested
decision, Nor did the EMA conduct the slightest weighing up in order to
determine whether there was a specific overriding public interest justifying
its disclosure. Instead, contrary to its earlier consistent decision-making
practice, the EMA applied an inflexible, purely mechanical policy
approach of complete disclosure of the disputed documents, on the basis
of an alleged automatic priority in favour of the general public interest in
transparency."
Rn 46: "... the EMA failed completely to address those detailed
arguments in the contested decision. The contested decision is thus
based on an inflexible policy favouring disclosure."
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Pending Court Case – InterMune vs EMA – General Court’s view in the
decision on the interim measures, T-73/13 II
Rn 52: "... This involves a question of principle affecting the functioning
of the pharmaceuticals and biotechnology sector in Europe and
worldwide..."
Rn 53: "... but rather requires an in-depth examination in the context of
the main proceedings. At that time, the Court, when it adjudicates upon the
substance, will have to examine, inter alia, the possible relevance for
resolving the dispute in the main proceedings of the case-law relied upon
by the applicants in order to justify the confidential treatment to be given to
the information at issue, namely Commission v Éditions Odile Jacob."
Rn 54: "... In any event, it is not obvious from the documents in the file
that, following that weighing up of interests, the balance will clearly be
in favour of the public interest defended by the EMA."
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Industry’s readiness to share data - Efpia/PhRMA Principles for
responsible Clinical Trial Data Sharing
• Commitment 1: Enhancing Data Sharing with Researchers
Anonymized patient-level data, study-level data, protocols, and complete clinical
study reports (CSRs);
Upon request from qualified researchers;
Researchers encouraged to publish results.
• Commitment 2: Enhancing Public Access to Clinical Study Information
Following approval in the US and EU;
Companies will post Clinical Study Report (CSR) synopses, at a minimum;
Full CSRs available to researchers under terms of Commitment 1.
• Commitment 3:Sharing Results with Patients who Participate in Clinical Trials
Provide factual summary of clinical trial results to research participants;
PhRMA and member companies will work with regulators to facilitate appropriate
communications to patients;
Ensure that summaries are not considered pre-approval promotion;
Explore appropriate communications mechanisms (e.g., through investigators,
web sites, and other means).
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EUCOPE Position on protection of Commercially Confidential Information
• It is generally acknowledged that clinical trial data may contain commercially
confidential information;
• Responsible public bodies including EMA carefully assess document by
document whether or not a piece of information must be considered commercially
confidential;
• The consultation of the marketing authorisation holder before disclosure
remains mandatory not only where third parties’ request access to this information
but also where the information is proactively disclosed by EMA;
• It is furthermore acknowledged that the disclosure of commercially confidential
information is not per se justified by an overriding public interest but that it has
to be decided on a case-by-case basis under participation of the marketing
authorisation holder whether the disclosure of commercially confidential data is
justified by an overriding public interest;
• No data will be disclosed before the grant of the marketing authorisation.
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C. Bindungswirkung der Ausweisung als
“Orphan Medicinal Product”
Superiority of EU Law over national
• The CJEU has held in the “Masterfoods Ltd. v. HB Ice Cream Ltd. et al”
decision that:
“It is also clear from the case-law of the Court that the Member States'
duty under Article 5 of the EC Treaty to take all appropriate measures,
whether general or particular, to ensure fulfilment of the obligations
arising from Community law and to abstain from any measure which
could jeopardise the attainment of the objectives of the Treaty is binding
on all the authorities of Member States ...”
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Price Regulation at National Level - Competency
Limits towards Member States‘ Competency on Price Regulation
• This principle holds true irrespectively of the competency of the Member States
to control their healthcare spending and regulate prices of medicinal products.
Article 168(7) TFEU provides the following:
“Union action shall respect the responsibilities of the Member States for the
definition of their health policy and for the organisation and delivery of health
services and medical care. The responsibilities of the Member States shall
include the management of health services and medical care and the allocation
of the resources assigned to them.“
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Restrictions on National Competency
• The CJEU recently reiterated this principle in case C-185/10
(Commission/Poland):
“It must be noted in that respect, first, that although EU law does not detract from
the power of the Member States to organise their social security systems and to
adopt, in particular, provisions intended to govern the consumption of
pharmaceutical products in order to promote the financial stability of their
healthcare insurance schemes, the Member States must, however, comply
with EU law in exercising that power (Joined Cases C-352/07 to C-356/07, C-
365/07 to C-367/07 and C-400/07 A. Menarini Industrie Farmaceutiche Riunite
and Others [2009] ECR I-2495, paragraphs 19 and 20).“
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EU decisions – Operative Part and Reasons
• Generally, only the operative part has a binding effect.
• An assessment of whether or not the criteria for an orphan designation
are fulfilled is not part of the operative part of the Commission’s decision.
• Nevertheless, the CJEU and the General Court have also decided on the
question whether the grounds of a decision can produce binding legal
effects. In a decision of 15 May 1997 the CJEU held that (emphasis
added):
“..., it should be stated that the operative part of an act is indissociably
linked to the statement of reasons for it, so that, when it has to be
interpreted, account must be taken of the reasons which led to its adoption.”
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EU decisions – Operative Part and Reasons
• Furthermore, in a judgement issued on 20 November 2002 (T-251/00)
the General Court stated that:
“Although the courts have consistently held that only the operative part
of an act is capable of producing binding legal effects and, thereby, of
having adverse effects, nevertheless the statement of the reasons for an
act is indispensable for determining the exact meaning of what is stated
in the operative part.”
• Accordingly, although it is only the operative part that is legally binding,
the extent of the binding effect has to be of the grounds that led to the
decision.
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EU decisions – Scope of the Commission’s decision
• The Commission’s decision to grant an orphan designation is based upon the
respective opinion of the Committee for Orphan Medicinal Products (COMP)
which examines any application.
• Article 3 (1) Regulation (EC) No 141/2000:
• To qualify for an orphan designation, a medicinal product:
must be intended for the treatment, prevention or diagnosis of a disease that
is life-threatening or chronically debilitating and the prevalence of the
condition in the EU must not be more than 5 in 10,000; or
that it is intended for the diagnosis, prevention or treatment of a life-
threatening, seriously debilitating or serious and chronic condition in the
Community and that without incentives it is unlikely that marketing of the
medicinal product would generate sufficient returns to justify the investment
needed for its development; and
no satisfactory method of diagnosis, prevention or treatment of the
condition concerned can be authorised, or, if such a method exists, the
medicine must be of significant benefit to those affected by the
condition.
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Binding Effect of Orphan Designation on Member States – Re-
Assessment by the EMA
• Re-Assessment of Criteria of Article 3 Regulation (EC) No 141/2000
foreseen in EU law
• The fact that the findings of the orphan designation cannot be challenged by
Member States‘ authorities alone is also established in Article 8(2) Regulation
(EC) No 141/2000.
• Article 8(2) Regulation (EC) No 141/2000 reads as follows:
• “This period may however be reduced to six years if, at the end of the fifth year, it
is established, in respect of the medicinal product concerned, that the criteria laid
down in Article 3 are no longer met, inter alia, where it is shown on the basis of
available evidence that the product is sufficiently profitable not to justify
maintenance of market exclusivity. To that end, a Member State shall inform
the Agency that the criterion on the basis of which market exclusivity was granted
may not be met and the Agency shall then initiate the procedure laid down in
Article 5. The sponsor shall provide the Agency with the information necessary
for that purpose.“
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Binding Effect of Orphan Designation on Member States – Re-
Assessment by the EMA
• Article 8(2) of Regulation (EC) No 141/2000 requires the Member State to
substantiate its doubts concerning the profitability of the product and submit
appropriate data to justify these doubts in order to initiate the procedure:
“The Member State in question should provide the rationale for its doubts and
include appropriate data justifying why at least one of the original designation
criteria of the orphan medicinal product concerned may no longer be met. In
preparing its information to the Agency, the Member State may use data which
supported the initial designation, held by the Agency.“
• The existence and detailed codification of this procedure under EU law
underlines that the Member States may not re-assess the findings of the
orphan designation on their own initiative.
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Summary
1. Member States are bound by the European Commission’s decision to designate a
medicinal product as an orphan medicinal product and may not question this decision or the
reasons on which the decision is based.
2. For legal reasons, it is not possible to artificially split indications in order to receive the
benefits of an orphan medicinal product marketing authorisation.
3. The German legislation followed the principle of precedence of EU law partly by
introducing individual provisions in the SGB V for orphan medicinal products with a yearly
turnover of less than EUR 50 million within the GKV. This necessary incentive could serve as an
example for other EU Member States as it is in compliance with binding provisions of EU law and
respects the orphan designation granted under Regulation (EC) No 141/2000.
4. For legal reasons this necessary incentive should be extended to all orphan medicinal
products rather than being reduced to a threshold of EUR 30 or EUR 25 million. Any
complete denial of an additional benefit of an orphan medicinal product authorised under EU law
in national pricing and reimbursement decisions is likely.
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Vielen Dank für Ihre Aufmerksamkeit
Dr. Alexander Natz, LL.M.
Director General
European Confederation of Pharmaceutical Entrepreneurs
(EUCOPE)
Rue d‘Arlon 50
1000 Brussels / Belgium
Tel.: 0032.2.290.8671