REPUBLIC OF SLOVENIA MINISTRY OF HEALTH AGENCY FOR MEDICINAL PRODUCTS AND MEDICAL DEVICES

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REPUBLIC OF SLOVENIAMINISTRY OF HEALTHAGENCY
FOR MEDICINAL PRODUCTS AND MEDICAL DEVICES

• REGULATORY, PRICING AND REIMBURSEMENT STRATEGIES
• IN SLOVENIA
• Round Table Discussion
• Ljubljana
• November 2005

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REPUBLIC OF SLOVENIAMINISTRY OF HEALTHAGENCY
FOR MEDICINAL PRODUCTS AND MEDICAL DEVICES

• Assoc.Prof. Stanislav Primoic, Ph.D., M.Pharm.
• DIRECTOR

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Four steps of entry of a medicinal product to a
national market

• 
  procurement

public / institutional
reimbursement
3rd party payor / user
pricing
controlled / free market
DRA
Q,E,S
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Concepts (1/3)

• Price CZ
• Prescribing frequency fRp
• Expenditure PSZ

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Concepts (2/3)

• Manufacturer price (ex-factory, apprx.50-70)
• Wholesaler price (wholesale, apprx.. 2-15)
• Pharmacy price (retail
• EU margins ca. 10-40)
• SI fee for service)
• VAT
• Nationally regulated

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Concepts (3/3)

• Pharmacoepidemiologic exposure
• Measures of consumption
• DDD/1000 pop.
• No. prescriptions
• No. units
• Penetration rate of new MPs
• Regulation (Marketing Authorization)
• Reimbursement
• Public procurement
• Therapeutic guidelines (e.g. DRG, WHO etc.)

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The System
Govt EC DRAs
Health Insurance
Pharmacy
the patient
M.P.
the prescriber
The Media
pharma industry
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Source Schulz Information (DK)
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Area between the two curves grows
Technology Curve (Pharma-Investment-Linked)
?
Affordability Curve (GDP-linked)
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Consumption and public spending for medicines
Source ZZZS
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VirSchultz Information, DK 2004
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Svet GDP regresija
SLO
Vir OECD
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SI
Approximate level of SI max price level entered
to original picture by ARSZMP
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Systemic players

• Transnational National
• EU/EC-DGs/EUDRA/G10 Gatekeepers
• WTO
• WHO
• Professional Organizations Local Reps
• Companies Ibid.

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Proposals vs. Decision making

• Health Professionals

P
Govt
D
H.auth.
Organizations
Patient Groups
Civil Society
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EU DRUG REGULATORY AFFAIRS

• Legal platform
• Administrative procedures
• Scientific content and advice
• Information management
• Risk management
• International activity

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LEGAL ARCHITECTURE (1/2)Acquis

• Regulations (e.g. 2309/93/EEC, 726/2004/EC ) HL
• Directives (e.g. 2001/83/EC, 2004/27/EC) HL
• European Court of Justice Case Law HL
• European Pharmacopoeia Monographs HL
• Guidelines SL
• Notice to Applicants SL
• EudraLex
• http//pharmacos.eudra.org/

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LEGAL ARCHITECTURE (2/2)National

• Medicinal Products legislation
• (based on EU Acquis, i.e. SI ZZMP and bylaws)
• Pharmacy Legislation
• Health Care and Health Insurance Legislation
• Pricing Reimbursement pf MPs
• Radiation Safety legislation
• National Guidelines (for use of medicines)

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DRUG REGULATORY AUTHORITIES IN THE EU

• CENTRAL AGENCY
• EMEA European Medicines Agency
• NATIONAL DRAs
• MHRA (UK), AFSSAPS (F), BfArM (D), ARSZMP (SLO),
  ...
• Functional connections HoA, MRFG, xIG, ICH
• SUPPORTIVE STRUCTURES
• EDQM / European Pharmacopoeia
• OMCL Network
• PIC

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AUTHORIZATION PROCEDURES IN THE EU

• CP Centralized Procedure
• EMEA
• MRP Mutual Recognition Procedure
• National Agencies Mutual Recognition
  Facilitation Group
• Reference Member State - RMS
• Concerned Member State(s) CMS
• National Procedure
• National Agencies

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AUTHORIZATION PROCEDURES IN THE EU

• Pre-authorization procedures
• Clinical Trials Authorization / Notification
• Manufacturing Authorization
• Wholesale Authorization
• Marketing Authorization
• Post-authorization procedures
• Variations (Type I, Type II, New Application/Line
  Extension )
• Renewals
• Pharmacovigilance
• Periodic Safety Update Reports (PSURs)
• Individual Case Safety Reports

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RISK MANAGEMENT

• Detection
• Assessment
• Management / Measures
• Reduction / Minimization
• Communication (RAS)
• PHARMACOVIGILANCE

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Agency for Medicinal Products and Medical
Devicesof the Republic of SloveniaA R S Z M P
Facts and Figures

• Constitutive Body within the Ministry of Health
• 34 employees
• First Established in 1996 (Office for Medicinal
  Products)
• Founded by the Medicinal Products and Medical
  Devices Act (2000) and by the Governmental Decree
  on Constitutive Bodies of the Ministries (2003)
• Restructured in 2004 into current sectorial
  structure
• Accent on institutional cooperation (OMCL,
  experts)
• Financed from (and contributing to) the State
  Budget
• Annual budget of approx. 1.1 MIO
• 40 administrative procedures
• Processing 10000 applications annually

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Agency for Medicinal Products and Medical
Devicesof the Republic of SloveniaA R S Z M P
Director
Consultative collegium
Regulatory Sector for Medicinal Products and
Medical Devices for Veterinary Use
Regulatory Sector for Corporate Activity Affairs

Regulatory Sector for Medicinal Products and
Medical Devices for Human Use
Pharmacoeconomic Sector
Pharmaceutical Inspection
Internal organization and systemization decree
(February 2004)
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CHMP
Quality WP
Biotechnology WP
Safety WP
CHMP Working Parties
Efficacy WP
Vaccine WP
Blood products WP
Pharmacovigilance WP
Gene therapy WP
Scientific advice WP
specific ad hoc working groups when needed
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Generic and Biosimilar Products

• Dir. 2004/27/EC (nov 2005) generic medicinal
  product (now essentially similar) shall mean a
  medicinal product which has the same qualitative
  and quantitative composition in active substances
  and the same pharmaceutical form as the reference
  medicinal product, and whose bioequivalence with
  the reference medicinal product has been
  demonstrated by appropriate bioavailability
  studies. The different salts, esters, ethers,
  isomers, mixtures of isomers, complexes or
  derivatives of an active substance shall be
  considered to be the same active substance,
  unless they differ significantly in properties
  with regard to safety and/or efficacy.

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Generic and Biosimilar Products
Chemicals
Recombinant DNA technology
Blood- Derived MP
Advanced therapy
Immunolo gicals
C o m p l e x i t y
Full dossier
Generic (essentially similar)
Biosimilar
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New EU Member States are they indeed so special?

• emerging from transition mid-to-low EU GDP
• EU Enlargement harmonizing regulatory system
• implemented EU MP and IP legislation
• substantial capacity of the overall market
• BUT Small national markets
• BUT Specific national materia medica
• BUT Specific pricing and reimbursement
  arrangements

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Making of a National Drug Policy

• Spending vs. Procurement Quotas for
  Pharmaceuticals
• Adjustments for New Technologies
• Therapeutic guidelines
• Generics Policy
• Parallel Imports Policy
• OTC Policy
• Drug Advertizing Policy

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Industry Makers of Choice

• Incentives to bring Products to a National
  Market
• (as seen from a regulators point of view)
• Positive vs. Negative (as per country)
• Market Capacity
• Market Perspective (PR, Penetration)
• Corporate Citizenship
• Sytemic Barriers
• IP Issues
• Ethical Considerations

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SLOVENIA PR Highlights

• Status of implementation of 89/105/EEC
• transparent
• non discriminatory
• appeal mechanism in force
• 90 d 90d (60d) timeline compliant
• concerns all drugs, but in practice otc are not
  controlled

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SLOVENIA Pricing Highlights

• Price Regulation
• comparative price system (DIF)
• 85 of average published wholesale prices
  (sourcesRote Liste, Vidal, Inf.Farmaceutico)
• negotiations up to 100 possible
• innovative to be compared with innovative,
  generic with generic
• generic substitution possible since 2003,
  physicians veto allowed
• generic prescribing possible but not used

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Apprx. Position of SI in 2003
Source Schulz Information DK. Note added to
original picture by ARSZMP
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top-100 medicines

• wholesale price index 2004/2003
• Mean 0,995
• STD 0,079
• MIN 0,70
• MAX 1,15
• trends of indices over 2001/2004
• (regression of annual growth index in the time
  period)
• slope gt0 in 78/100 MPs
• naklon gt 0,05 in 15/100 MPs
• max 0,14
• min -0,24

medicines
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RS Reimbursement Highlights

• health insurance institution insurance
  companies
• positive list (P)
• compulsory insurance covers 75, voluntary
  insurance or out of the pocket covers 25
• intermediate list (V)
• compulsory insurance covers 25, voluntary
  insurance or out of the pocket covers 75
• categories to be reimbursed 100 (children,
  pregnant women, chronic diseases)
• apprx. 1500 medicinal products (out of apprx.
  3000 authorized are reimbursed)

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RS Referencing of Medicinal Products

• Maximal Attributed Value in multisource domain
• Relative Therapeutic Value in innovative domain
• Positive (P), Intermediate (V) lists updated
  semi-annually
• reference price system to be upgraded
• within-INN referencing (i.e. all nifedipine
  products)
• among-INN referencing (i.e. all calcium-blockers)
• savings effect 5-10 of market value

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SI state of play

• Rules on wholesale prices of MPs
• ARSZMP pricing surveillance, monitoring,
  measures
• Rules of the Compulsory Health Insurance
• Decision on classification to reimbursement lists
• Rules on reimbursement procedures
• Committee for reimbursement (advisory)
• Mutually interchangeable medicines, MZZNPV
• Health insurance Institution price negotiations
• Consent of the Minister of Health

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• In Q4 2003, Slovenia introduced the system of
  generic substitution and generic prescribing
  based on the mutual interchangeable medicinal
  products. ARSZMP has published an official list
  of mutually interchangeable medicinal products
  (MIMP) in the Official Gazette of the Republic of
  Slovenia on Oct 10th, 2003. In line with it, one
  week later, ZZZS has published a derivative list
  of mutually interchangeable medicinal products
  with their maximum attributed values (MAVs).

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• The two lists are, along with adaptations of the
  pertaining drug classification bylaw and rules of
  the compulsory health insurance published over
  the period of six months, the legal basis of
  the new system of classification of medicines on
  the basis of their nonproprietary names (INNs),
  INN-prescribing by physicians, and generic
  substitution by pharmacists.

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•  The MIMP is a list of essentially similar
  medicinal products, which, within the frame of
  the same active ingredient(s), same strength,
  same or comparable pharmaceutical form and same
  or comparable packing, can be mutually
  interchanged according to the rules. The
  definition of essential similarity and the
  technical requirements for the recognition of
  bioequivalence of the products follow that of
  the EMEA guideline on bioequivalence studies of
  2002.

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SITOP-100 medicines at ATC1
levelMZZ-mutually interchangeable MPs list
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SI Average price increase index 2001-2004 at
ATC1- level
TOP100
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SI Average price growth index 2004/2003 for
TOP-100 medicines
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Conclusions

• All member states in the enlarged EU will need to
  continue to develop greater connectivity between
  regulatory, policy departments and 3rd party
  payors in order to assure transparent and
  efficient means for access to medicines
• Health insurance is likely to develop new
  products to disburden public funds
• Cost containment measures will remain to be a
  principal mechanism assuring access to innovative
  medicinal products
• Slovenia is in a bridging position between old
  and new MSs

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Conclusions 2

• Prices of principal MPs in SI are relatively
  stable and largely remain within the inflation
  range
• Risks and Challenges in PR domain are increasing
• ARSZMP developing its Sector for
  Pharmacoeconomics in connection with external
  expertise.
• Information exchange within EU and Telematic
  support in the PR area is crucial
• Development of generic substitution towards
  therapeutic groups referencig is needed.
• Added therapeutic value assessment to be shared
  within EU MSs