Polepharma Meetings
Récents développements législatifs en Europe:
Exemple de l‘industrie pharmaceutique allemande
19.09.2012, Dreux
Dr. Alexander Natz
I. Pricing and Reimbursement strategies in different Member
States: Germany
II. Revision of the Transparency Directive 89/105/EEC
Outlook: Regulations / Directives / Guidelines in 2012 - 2014
New legislation / delegated acts:
Transparency directive (COM proposal 01.03.2012)
Clinical trials (COM proposal 17.07.2012)
Patient Information (COM proposal 10.02.2012)
Horizon 2020 (COM proposal 30.11.2011)
Medical devices / In-vitro-diagnostics (COM proposal likely on 26.09.2012)
Delegated acts anti-counterfeit directive (likely in 2014)
Delegated / implementing acts pharmacovigilance (02.07.2012)
Review EU guideline good distribution practice (GDP)
Plus: Recast Directive 2001/82/EC, EMA fee regulation, Variations Reg.
(EC) 1234/2008 …
EUCOPE general objectives (see: www.eucope.org)
Eucope: the mid-sized companies perspective
EUCOPE represents
900+ mid-sized companies via the associations EMIG, BPI, BioDeutschland,
SwedenBio, IML, PEF
Board represents companies from Sweden, UK, Bulgaria, Italy, Greece,
Germany, the Netherlands …
Companies represented: B. Braun, SigmaTau, Ferring, Grifols, Biogen Idec
Celgene, Alexion, …
Recognized stakeholder by EMA, European Commission and the European
Innovative often family owned companies
EUCOPE Positions
EU Relevance in the context of Directive 2011/62/EU
• In the EU, approx. 30% of manufacturers of prescription medicines fall
within the definition of SME (Commission Impact Assessment,
SEC(2008)2674,p. 70).
EUCOPE Activities
Monitoring - Networking - Lobbying - Information - Communication:
Establish a network of European pharmaceutical entrepreneurs
Represent their interests at the EU institutions
Promote business opportunities given by the Community market
Create visibility by international conferences and press releases
Deliver a regular update on relevant dossiers
Maintain and extent contacts with key MEPs and key Commission officials
Participate in Consultations, Comitology and Expert Groups
Co-operate with other Associations and stakeholders
14 new EUCOPE Members in 2011
17 New Members in 2012
Sigma Tau Arzneimittel GmbH (http://www.sigma-tau.de/en)
Otsuka Novel Products GmbH (http://www.otsuka.de/)
Ferring Holding SA (http://www.ferring.com/en/home.htm)
IML (Innovativa Mindre Life Science Bolag - Swedish association for small
and medium-sized Swedish life science firms active in R&D)
Atlantis Healthcare Group (http://www.atlantishealthcare.com/)
SidleyAustin LLP (http://www.sidley.com/)
Weimer Pharma GmbH (http://www.weimer.de/en/home.html)
SwedenBIO (www.swedenbio.se)
PEF (Greek Association of mid sized innovative companies)
Miltenyi Biotech (http://www.miltenyibiotec.com)
Grifols (http://www.grifols.de)
Ursapharm (http://www.ursapharm.de/de/home/)
Diapharm (http://www.diapharm.com/deutsch/index.html)
Fasken Martineau (http://www.fasken.com/en/home/)
I. Pricing and Reimbursement in
Germany: Pricing and reimbursement of innovative
pharmaceuticals from 1.1.2011 (AMNOG)
Mandatory discounts up to 16 % (from 6 %) for three years
Extension of mandatory discounts to private insurers
Early benefit assessment / mandatory discount negotiations
– extra benefit (+): agreed discount mandatory from 2nd year
– extra benefit (-): amount is set acc. to costs of comparative therapy
New package sizes / generic substitution
Impact / Outlook:
intended savings of 2.2 billion € / year, i.e. almost 7% compared to the overall
spending of the statutory health insurers (SHI) in 2009 for pharmaceuticals (30
billion €)
Overview of the early benefit assessment procedure
Pricing: Impact of other EU prices on German prices / Country
15 countries set by Arbitration Board:
Belgium, Denmark, Finland, France, Greece, UK, Ireland, Italy, the Netherlands,
Austria, Portugal, Sweden, Slovakia, Spain and the Czech Republic.
Possibility for adaption once per year (with effect from 1.1.2014 for the first time).
Principles set by Arbitration Board for further development of the country basket
– Not limited to the Euro countries, but to all EEA countries.
– The country basket should cover circa 80 percent of the population of all
the EEA countries (excluding Germany).
– The basket should include such countries with a comparable economic
standing as Germany (GDP per capita in purchasing power standards,
First price negotiation, § 130b SGB V: state of play (June 2012)
First price negotiation between GKV-Spitzenverband and MAH:
Ticagrelor (Brilique) by AstraZeneca
Exact price / rebate confidential until contract finalized
Agreed price / rebate applies retroactively as of 1.1.2012
Agreement was to be expected because German price was already low
compared to other EU countries
Some companies (e.g. Pfizer, GlaxoSmithKline, Boehringer Ingelheim and Lilly)
have ceased / postponed negotiations with GBA over diverging views on
apropriate comparator
Dossier for early benefit assessment
§ 35a (1) 10 SGB V
• Authorized therapeutic indications
 (+)
• Patient Benefit (medical benefit)
 (-)
• Additional Benefit in relation to appropriate comparative therapy (additional medical
benefits, added value)
 (-)
• Costs of therapy to statutory health insurance
 (+)
• Quantification of the number of patients and/or definition of limits for the treatment
of potential patient groups
 (+)
• Description of the requirements for quality-assured application
 (+)
Nonetheless, § 12 (1) 1 of the GBA rules of procedure “the extent of the additional
benefit must be proven for the number of patients and patient groups, for
whom there is a therapeutically important additional benefit .”
 Prifenidon (Esbriet ®) case
HTA in Germany: Need for clarification for preparation of dossiers
HTA in Germany: Different choice of comparators by IQWiG and company
Germany: Disclosure of Discounts ?
Orphan drugs: First early benefit assessment by IQWiG (Pirfenidon)
Germany: AMNOG reform (16 AMG Amendment)
Germany: Weighting of country prices for international reference
pricing in Germany
28 June 2012: German Parliament passed the so-called 16th AMG Amendment
“the actual sales prices in other European countries while weighting the
respective turnover and purchasing power parities are taken into account.”
Justification: “to ensure comparability” of the prices.
Prices in larger countries such as France or the UK gain much more impact on
the price negotiations and price setting which is generally welcomed.
Prices in lager Member States such as France (65 Mio inhabitants) should have
five or six times more influence than e.g. in Greece (11 Mio inhabitants) if the
turnover of the product equals this ratio.
This change entered into force already on 28 June and thus applies to all
upcoming price negotiations.
Views of the GKV-Spitzenverband
Effect of the GBA decision for the price negotiations
• The GBA decision is considered as binding for the price negotiation by the GKVSpitzenverband. There is no possibility for companies to present additional
scientific data during the price negotiations. However, this does not apply to
data concerning margins and prices in other European countries. It is likely
that this view is shared by the courts.
Decisive criteria for the price negotiations
Relevant criteria the framework agreement states (Art. 6 Rahmenvertrag):
• the GBA decision on additional benefit
• the early benefit assessment conducted by IQWiG and the dossier submitted by
the company
• annual therapy costs of comparable medicinal products
• the 'actual sales price' in certain European countries (country basket)
It is not clear yet what is to be considered as 'actual sales price'.
Pirfenidone: First OMP HTA benefit assessment (§ 35a SGB V)
IQWiG (Institute for Quality and Efficiency in Health Care) saw no quantifiable
additional benefit for treating midiopathic pulmonary fibrosis (IPF) over
comparators – but assessment is (just) a recommendation for the final G-BA
15.03.12: GBA (Joint Federal Committee) decision: a non-quantifiable additional
benefit exists for Esbriet used in adults to treat mild to moderate idiopathic
pulmonary fibrosis (IPF)  deviates significantly from the IQWiG
GBA assessment forms the basis for the subsequent price negotiations on the
reimbursement amount. In case no consent is reached within 6 months an
arbitration committee will set a reimbursement amount, which is applicable from
month 13 after entry into market (§130b SGB V).
Case of Pirfenidone/Esbriet as precedent for the assessment of other OMPs:
OMP with a yearly turnover of less than 50 Mio. Euro in Germany additional medical
benefit neither has to be proven by the marketing authorization holder nor to be
assessed by IQWiG/GBA.
IQWiG assessments: state of play (01.06.2012)
Negative Decisions
Positive Decisions
Microbial Collagenase from
Clostridium histolyticum
Azilsartan Medoxomil (as potassium
IQWiG assessments: state of play (01.06.2012)
Pending Cases:
In preparation of decisions:
Apixaban / Belatacept / Emtricitabin, Rilpivirin, Tenofovirdisoproxil / Tafamidis /
Meglumin / Rilpivirin / Extract from Cannabis Sativa
Consultation period:
Belimumab / Fampridin / Ipilimumab
Vandetanib / Vemurafenib
No status:
Olmesartanmedoxomil, Amlodipin, Hydrochlorothiazid
IQWiG assessments: Recent decisions
15.03.2012: Tafamidis & relevant orphan drugs  will be assessed on the basis
of the marketing authorization and the studies on which it was based
29.03.2012: Cabazitaxel & relevant diagnostic drugs  the GBA favors the
inclusion of diagnostic drugs in the process of early benefit assessment
16.04.2012: Rilpivrin (Edurant), Belatecept (Nulojix) and Emtricitabin / Rilpivrin /
Tenofovirdisoproxil (Eviplera)  It is remarkable that in two cases the IQWiG
(partially) followed the company’s deviation from the comparator set by the
02.05.2012: Belimumab (Benlysta), Fampridine (Fampyra), Ipilimumab (Yervoy)
 The procedures show that even in case the pharmaceutical company
follows the comparator therapy set by the GBA the IQWiG can deny any
additional benefit by declaring studies relevant or irrelevant regarding the
“optimized” comparator therapy
GBA: state of play (June 2012)
Most recent decisions: assessments of Retigabin and Alsikiren / Amlodipin
GBA follows IQWIQ decision: No additional benefit
Result is based on the finding that the MAH deviated from the comparator set
by the GBA
MAHs are given the option to submit a new dossier within one year
– GBA sees HTA still as “learning system”
– The new dossier has to include the comparator set by the GBA
Assessment of “pre-AMNOG products” (I) - Gliptines
GBA decided for the first time to request pre-AMNOG products to undergo
early benefit procedures
 After linagliptin, early benefit assessment for all other DPP-4 inhibitors in
German market (sitagliptin, vildagliptin, saxagliptin)
 Parallel evaluation, deadline for dossiers submission: 31.12.2012
 Until delivery of requests (30.9.): consultation with GBA possible
What would that mean:
More products already marketed before AMNOG could be subjected to early
benefit assessment according to indication groups
Assessment of “pre-AMNOG products” (II) - Outlook
GBA announced that there would be only a "limited start" to look at the preAMNOG market, referring to two arguments:
1) Avoidance of competition distortions: manufacturer can still submit a
dossier with the comparator set by the GBA at a later point in time
despite the opt-out of the procedure for linagliptin
2) High prevalence of indication (type 2 diabetes) and sales
GBA considers this call as: singular event with no further implication for preAMNOG market
Danger of future repetition when companies decide to opt out of the procedure
and take legal action against the setting of the comparator by GBA
Decisive for companies: close watch on procedures regarding (potential)
competitor products
Open Questions
Opt Out Scenario in AMNOG:
• What happens if procedure has been initiated?
• Does that mean that there is automatically a price set at the end of the
• Or: does the company have the opportunity to opt out of the procedure
and thereby ending the procedure?
Our first analysis points towards a situation whereby the company cannot stop
the procedure but we will clarify this in due course
So what happens to old products already in the market?
How likely is it that GBA picks up “old” product?
Example Netherlands: Price reductions through tenders
Price reductions since 01.06.2008 for the six top-selling products
according to European Commission:
Source: European Commission, Pharmaceutical Secor
Inquiry, Final Report, 8.7.2009, para 376.
II. Revision of Directive 89/105/EEC
(Transparency Directive)
Transparency Directive: A step in the right direction
Commission proposal COM(2012)84 – Timeline for Adoption
– 1 March 2012: Commission’s Proposal published
– 19 April 2012: ENVI: Antonyia Parvanova (ALDE) appointed as Rapporteur
(Shadow Rapporteurs: Zofija Mazej (EPP) and Nessa Childers (S&D)
– IMCO (Raporteur Cristian Silviu BUŞOI - ALDE) to give opinion, other
Committees (EMPL, ITRE, JURI) declined
19 September 2012: Presentation of Draft Report in ENVI
3 October 2012: Deadline for tabling amendments
6 November 2012: Discussion in ENVI
28 November 2012: ENVI to adopt report
15 January 2013: Indicative Plenary sitting date/1st Reading
Spring 2013: Earliest Adoption (Member States to amend national laws within 12
Key Topics
 Confidentiality of Managed Entry Agreements (MEA)
 Scope of the directive (voluntary contractual agreements)
 Non-reassessment clause and orphan medicinal products
 Enforcement procedures
EUCOPE Positions - Commission proposal COM (2012) 84
Possible changes:
 Transfer of ECJ case law (demand-side-related measures) - positive
 No mandatory EU list of national prices - positive
 HTA-procedures in scope of Directive - positive
 Results of MA (Q/S/E) shall not be put in question in P&R decision - positive
 Time limits for P&R decisions (15/30 generics - 60/120 innovative medicine)
 Managed entry agreements remain confidential - positive
 Public procurement law (not Transparency Directive) governs tenders
 No inclusion of medical devices - negative
 No specific provision on personalized / stratified medicine - negative
No mandatory EU price list / Confidentiality of MEA
Commission proposal COM(2012)84 includes the following aspects:
• Proposal does not foresee a mandatory EU price list aiming to compare listed/
rebated prices among Member States which is a positive result. However, Member
States remain free to compare prices / introduce external reference pricing.
• Contractual agreements and managed entry agreements remain excluded from
the directive, if on a voluntary basis.
• EU law will not require to publish the content of price negotiations with payers
which is correct and most important from our perspective. However, Member
States - again - remain free to require disclosure and bypass confidentiality.
• Cost containment measures under public procurement law (tenders in generic
markets/ some medical devices) remain outside the scope of the directive (Art.
1). This is consistent since public procurement law guarantees detailed procedural
rights for bidders and protects the same objectives (objectivity and equal
HTA definition / demand-side-related measures / time limits
• The directive defines for the first time the term health technology assessment
as “an assessment of the relative efficacy or of the short- and long-term
effectiveness of the medicinal product compared to other health technologies in
use for treating the associated condition” (Art. 2).
• HTA agreements (such as the early benefit assessment in Germany by the GBA)
therefore fall in the scope of the directive
• Demand-side-related measures (incentives to physicians such as me-too lists)
are in the scope of the directive (see ECJ, ABPI case C-62/09) which we see
• It is positive that the time limits for pricing and reimbursement are reduced for
both generic (15/30 days) and innovative medicinal products (60/120 days). In
cases where national authorities subject medicinal products to HTA procedures the
time-limits are longer (90/180 days).
Notification of national measures / No reassessment of Q/S/E/B
• Art. 15 foresees mandatory consultations of interested parties at national level
and the publication of the results.
• Furthermore a notification procedure for draft national measures is foreseen
which would oblige the MS (and national HTA bodies such NICE or GBA) to inform
the Commission of any changes of their rules of procedure before implementation
(“immediately”) (Art. 16). While we consider it as an important aspect that a
preliminary check of the compliance with the provisions of the ‘Transparency
Directive’ is introduced, we think that the notified measures should remain
confidential. The Commission also has no right of veto (“The observations of the
Commission shall be taken into account as far as possible …”).
• Results
of the marketing authorization (quality, safety, efficacy,
bioequivalence) shall not be reassessed in HTA decisions which is a positive
 Possible changes:
 On HTA:
“Member States shall refrain from requesting data and proof of quality, safety and
efficacy or bioequivalence of the medicinal product concerned beyond the
elements already assessed in the marketing authorization.”
 On IPR:
”The protection of industrial and intellectual property rights cannot be a valid ground
to refuse, suspend or revoke decisions relating to the price of a medicinal product
or its inclusion within the public health insurance system.”
Scope (I)
The directive applies to “any national, regional or local measure, whether laid
down by law, regulation or administrative action, to control the prices of
medicinal products for human use or to determine the range of medicinal
products covered by public health insurance systems, including the extent
and conditions of their coverage” (Art. 1 (1))
The Directive shall not apply to
voluntary contractual agreements between public authorities and the MAH
that have as their object to enable the effective provision of this medicine to
patients under specific conditions (Art. 1 (2) (a))
national measures intended to determine the prices or the coverage of
medicinal products by public health insurance systems which are subject to
national or Union legislation on public procurement (Art. 1 (2) (b))
Scope (II)
The Commission proposal covers the following P&R measures explicitly:
Price approval (Art. 3)
Price increase (Art. 4)
Price freeze and price reduction (Art. 5)
Controls on profits (Art. 6)
Inclusion of medicinal products in health insurance systems (Art. 7)
Exclusion of medicinal products from health insurance systems (Art. 9)
Classification of medicinal products in view of their inclusion in health
insurance systems (Art. 10)
Measures to control or promote the prescription of specific medicinal
products (Art. 11)
Scope (III)
Open questions:
It remains unclear whether the procedural requirements of the Transparency
Directive apply to a HTA-decision itself.
Which agreements will be considered as voluntary contractual agreements?
To which (non-voluntary) agreements apply mirror-wise the requirements of the
Transparency Directive)?
Does the proposal require to publish the content of price negotiations
with payers?
(New) Provisions to improve transparency
MS shall publish and communicate to the Commission criteria for decisionmaking process ( Art. 3 (8), 7 (8), 10 (2), 10 (3))
MS shall establish in detail the particulars and documents to be submitted
by applicant (Art. 3 (4), 4 (4), 7 (3))
Ms shall not request any additional information which is not explicitly
required under national legislation or administrative guidelines in the
framework of P&R ( Art. 3 (5), 4 (4), 7 (5))
The requirement of legal remedies has to include effective judicial remedies
(e. g. recital 13)
MS shall not re-assess the elements on which the marketing authorisation
is based, including the quality, safety, efficacy or bioequivalence of the medicinal
product (Art. 13)
Dialogue and enforcement
Mandatory consultations of interested parties at national level and the
publication of the results (Art. 15)
MS shall immediately communicate to the Commission the draft measure
envisaged, together with the reasoning on which the measure is based. MS shall
take the observations of the Commission into account as far as possible. (Art. 16)
No right to veto for the Commission
A preliminary check by the Commission seems still helpful. However, the
notified measures should remain confidential.
Art. 8 introduces a remedies procedure in case of non-compliance with the time
limits related to the inclusion of medicinal products in health insurance systems.
Therefore MS shall designate an independent body that has the power to adopt
interim measures, award damages and impose a penalty payment
ECJ (C-62/09 – ABPI/MHRA – 22.04.2010) on Transparency
38 “Consequently, even though Directive 89/105 has as an underlying principle the
idea of minimum interference in the organisation by Member States of their
domestic social security policies (Case C-245/03 Merck, Sharp & Dohme [2005]
ECR I-637, paragraph 27), national public health authorities which adopt a
financial incentive scheme for the prescription of specific named medicinal
products are required in particular to make such a scheme public and to
make available … professionals in the pharmaceutical industry the
evaluations establishing the therapeutic equivalence of the active
substances available belonging to the therapeutic class covered by that
 demand side related measures fall under the Transparency Directive
 in case of comparisons: therapeutic equivalence has to be established +
has to be made transparent
EUCOPE position
• Commission proposal is a mostly positive result
• However, medical devices should have been included in the scope of the
directive and specific provisions
personalized/stratified medicines.
• EUCOPE welcomes most:
No mandatory EU price list
Contractual agreements and managed entry agreements remain excluded from
the directive, if on a voluntary basis
Results of the marketing authorization shall not be reassessed by HTA bodies
• Next steps
– Debate in European Parliament / Council is foreseen in 2012
– EUCOPE Debate in the EP on 21.6.2012
– Implementation by Member States likely in 2013/2014
Thank you for your attention!
Dr. Alexander Natz, LL.M.
Director General
European Confederation of Pharmaceutical Entrepreneurs
Rue d`Arlon 50
1000 Brussels / Belgium
Tel.: 0032.2.282.0475
[email protected]

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