ジェネリック医薬品市場の新たな動向と課題：2007年

Generic drugs (generics) are now an established part of pharmaceutical markets and healthcare policies around the world. According to IMS Health data, they already account for 63% of all prescriptions dispensed in the US, the world' s largest single pharmaceutical market.

The European Generic Medicines Association, the EGA, has predicted that, by the end of the decade, generics could account for 75% by volume of all pharmaceuticals sold in an expanded European Union (EU), with a total market value of € 21 billion.

This forecast takes into account both new Member States such as Poland and the Czech Republic that have a strong heritage of generic production from previously nationalised pharmaceutical industries, as well as Western European countries, such as France, Spain or Portugal, in which ballooning healthcare costs have finally persuaded governments to take more aggressive action to encourage the use of generics.

Seen in value terms - and generics remain very much about lower prices - the advances are less dramatic. In the fiercely competitive US market, for example, IMS Health estimated generic penetration by value to be around 11% in 2005. In the UK, the country with the highest value share that year - about 24%, excluding discounts - branded and unbranded generics made up 64% of the overall market by volume.

There is clearly plenty of room for further expansion of the generics sector, albeit in an environment where low-cost generics manufacturers from countries such as China and Brazil are remorselessly dragging down prices and some important markets, such as Japan, are still lagging significantly in their efforts to stimulate sales of generics.

IMS Health is forecasting generics sales growth of 13-14% worldwide in 2007, compared with 5-6% for the pharmaceutical market as a whole. Such growth would increase the value of the global generics market to $60-65 billion.

Two key factors are particularly fuelling this growth: European governments' efforts to slow the rise of healthcare costs and the string of patent expiries on key pharmaceutical brands in the US and other major markets.

Prescription drugs with aggregate sales of $51 billion faced patent expiry in the five years to 2006, IMS Health notes; the figure for the period between 1996 and 2000 is only $17 billion.

Table of Contents

ABBREVIATIONS

• 1.1 The origins of TRIPS
• 1.2 What TRIPS did
• 1.3 Before and after TRIPS
• 1.4 The consequences of TRIPS
  • 1.4.1 Proprietary rights and public health
  • 1.4.2 Brazil - conflicts
• 1.5 Data exclusivity
  • 1.5.1 Article 39.3: open to interpretation
• 1.6 The patent effect
  • 1.6.1 India and AIDS therapies
  • 1.6.2 Other countries and therapies
• 1.7 What' s in the box?
  • 1.7.1 Generics concession
• 1.8 Novartis' legal challenge
• 1.9 A step further
• 1.10 Difficult comparison
  • 1.10.1 Unravelling AIDS drug prices
• 1.11 Different priorities
• 1.12 Sanofi-Aventis' ASAQ concession
  • 1.12.1 Control strategy?
• 1.13 The bigger picture

• 2.1 The Bolar exemption
• 2.2 Compulsory licensing draws blood
  • 2.2.1 Compulsory licensing: already exploited
  • 2.2.2 The South African AIDS case
• 2.3 TRIPS Agreement and Public Health
  • ..... Parallel imports
  • ..... Compulsory licences
  • ..... Differential pricing
  • ..... Protection of test data
  • ..... Transitional arrangements
  • 2.3.1 The US and EU' s view
• 2.4 The Doha Declaration
  • ..... Parallel imports.
  • ..... Transition periods
  • ..... Compulsory licensing
• 2.4.1 Declaration on the TRIPS Agreement and Public Health

• 3.1 Back to the barricades
• 3.1.1 The Motta text
• 3.2 The 30 August decision
• 3.3 The 30 August provisions
• 3.3.1 Conditions for compulsory licensing
• 3.4 Double trouble
  • 3.4.1 Anti-diversion efforts
• 3.5 Economies of scale

• 4.1 Loose ends
  • 4.1.1 Rwanda sets the precedent
• 4.2 Mixed result in Canada
• 4.2.1 Canada' s limited list
• 4.3 The EU regulation
  • 4.3.1 Parliament' s response
• 4.4 The political debate over ratification
  • 4.4.1 Parliament dissents
• 4.5 The FTA threat
  • 4.5.1 Contrary to Doha?
    • ..... Delayed approval of generic drugs
    • ..... Required patent extensions
    • ..... Linked drug approvals to patent status
    • ..... Restricted compulsory licensing
    • ..... Prohibited parallel imports
    • ..... Expanded patent protection
• 4.6 US generic resistance
  • 4.6.1 Pressure on Guatemala
  • 4.6.2 New Trade Policy for America
  • 4.6.3 Industry responses
  • 4.6.4 Newly signed FTAs
• 4.6 More clashes over compulsory licensing
  • 4.6.1 Thailand and compulsory licensing
  • 4.6.2 A political rift in Europe
  • 4.6.3 Brazil and compulsory licensing
  • 4.6.4 A “chilling signal”
  • 4.6.5 The Philippine situation
• 4.7 Living with patents
  • ..... in China
  • ..... in India
• 4.8 India abroad
• 4.9 Tough enough for the US?
  • 4.9.1 Dr Reddy' s AmVaz setback
  • 4.9.2 Staying power?

• 5.1 A solid foundation
• 5.2 Consolidation abounds
• 5.3 Increasing sales
• 5.4 Pricing issues
  • 5.4.1.1 Vertical integration
  • 5.4.2 Optimism about US pricing
• 5.5 A healthy future?
• 5.6 The generic rationale
  • 5.6.1 The impact of Medicare
  • 5.6.2 Muted effect
  • 5.6.3 Generics will benefit
• 5.7 Drug pricing debate persists
• 5.5 Wal-Mart' s $4 generic offer

• 6.1 Modernising for generics
  • ..... The 180-day marketing exclusivity
  • ..... The 30-month stay
  • 6.1.1 Strategic alternative
  • 6.1.2 The FTC' s findings
  • 6.1.3 The FTC' s recommendations
• 6.2 Legislative responses
• 6.3 The FDA steps in
  • 6.3.1 The FDA' s final rule
  • 6.3.2 Speeding up generic approvals
• 6.4 Legal back-up
  • ..... 30-month stays
  • ..... Declaratory judgments
  • ..... 180-day exclusivity
  • ..... Counterclaims
  • ..... Notification of settlements
  • ..... Bioequivalence
  • ..... Anti-bundling
  • 6.4.1 FDA' s guidance for industry
• 6.5 Widening the gap
  • ..... Try again

• 7.1 Looking at Medicaid
• 7.2 The patent bounty
• 7.3 Case study: simvastatin
  • 7.3.1 Enter Sandoz...
  • 7.3.2 Enter Dr Reddy' s...
  • 7.3.3 “Legal bribes”?
• 7.4 US battle not over
  • 7.4.1 Medicaid again
  • 7.4.2 Final rule on drug price reporting
  • 7.4.3 Pharmacists hit
• 7.5 Authorising authorised generics
  • ..... Accelerating trend
  • 7.5.1 Playing both sides of the fence
  • 7.5.2 Undermining the 180-day exclusivity
  • 7.5.3 The FTC' s study of authorised generics
    • 7.5.3.1 Delayed action
  • 7.5.4 Pricing impact
    • ..... GPhA begs to differ
  • 7.5.5 A legal remedy?
    • ..... No legal basis
  • 7.5.6 Bills S. 438 and H.R. 806
• 7.6 Not so exclusive
  • 7.6.1 Multiple first applicants
  • 7.6.2 The Paxil judgement
• 7.7 The first-to-file system - Apotex calls for an overhaul
• 7.8 Patent settlements under the spotlight
  • 7.8.1 The reverse-payment investigation
    • ..... No headway for the FTC
  • 7.8.2 The Preserve Access to Affordable Generics Act
  • 7.8.3 More Congressional action
    • ..... Not in your interests
    • ..... A lenient view
• 7.9 Case study: Plavix
  • ..... An unusual series of events
  • 7.9.1 A tentative agreement
  • 7.9.2 Strategic blunder
    • ..... Valid and enforceable
• 7.10 More about Citizen Petitions
  • 7.10.1 A bifurcated system
  • 7.10.2 The FDA Revitalization Act
• 7.11 More trouble with patents
  • 7.11.1 First to invent or to file?
  • 7.11.2 Best mode requirement
  • 7.11.3 Start with the USPTO
• 7.12 The perils of biodefence
  • ..... Strong reservations
  • 7.12.1 A comfortable compromise
• 7.13 Clearing the backlog
  • 7.13.1 API suppliers - choose carefully
  • 7.13.2 The benefits of user fees
• 7.14 Towards a generic drug user-fee programme
  • 7.14.1 Not a magic bullet
  • 7.14.2 OGD is “overworked”; “overwhelmed”
  • 7.14.3 No programme yet
• 7.15 On the fast track for ‘first generics' and others

• 8.1 Everything changes
• 8.2 The EU: a singular not single market
• 8.3 Factors for growth
  • 8.3.1 Critical outcomes of the pharmaceutical review
  • 8.3.2 The impact of an aging population
  • 8.3.3 The cost saving effect
  • 8.3.4 The impact of patent expiries
• 8.4 More on cost-containment and pricing pressure
  • 8.4.1 A new pricing paradigm
• 8.5 Back to the pharmaceutical review: a fair compromise?
  • 8.5.1 Advances for the generics industry?
  • 8.5.2 Data exclusivity provisions: a difficult birth

• 9.1 Data exclusivity
  • 9.1.1 Explaining eight plus two plus one
• 9.2 Defining “significant clinical benefit”
• 9.3 The cost of the eight plus two plus one compromise
• 9.4 Against data exclusivity
  • ..... Who owns the data?
  • ..... Back door to market protection
• 9.5 Compensations of the legislation
  • 9.5.1 Derogations from eight plus two plus one
• 9.6 More ‘plus ones'
  • ..... What is ‘well-established' ?
  • 9.6.1 Data exclusivity for OTC switches
  • 9.6.2 National complications
• 9.7 Global Marketing Authorisation - a win for generics
  • 9.7.1 Court back-up
• 9.8 Defining generics
• 9.9 The European Reference Product
  • 9.9.1 The ECJ' s verdict on Generics UK/Losec
  • 9.9.2 Creative product removal
  • 9.9.3 Backdating European Reference Products

• 10.1 What Bolar allows
  • 10.1.1 The experimental-use exemption
  • 10.1.2 Disparity with the US Bolar clause
  • 10.1.3 Europe' s Bolar variations
    • 10.1.3.1 UK Bolar
    • 10.1.3.2 German Bolar
    • 10.1.3.3 Italian Bolar
  • 10.1.4 Stockpiling - another grey area
• 10.2 Bolar: a back door to patent linkage?
  • 10.2.1 Isolated case
• 10.3 A European patent solution?
  • 10.3.1 The EPLA solution
  • 10.3.2 An integrated approach
    • ..... The language barrier
• 10.4 Some harmony in SmPCs
  • 10.4.1 Usage patents
  • 10.4.2 ‘Carving out'
• 10.5 The name game
  • 10.5.1 Different generic names
• 10.6 Marketing Authorisation: which route to take?
  • 10.6.1 The European Commission' s draft guideline
  • 10.6.2 The EMEA' s draft guidance
  • 10.6.3 The ‘old' and ‘new' MRP
  • 10.6.4 Guideline on “serious risks to public health”
  • 10.6.5 What the decentralised route offers
    • ..... “Exceeded all our expectations”
• 10.7 Case study: Zalasta goes central
• 10.8 The ‘sunset clause'
• 10.9 What' s more... criminal measures and paediatric use
  • 10.9.1 IPRED II
    • ..... One size fits all
    • ..... Catching dolphins in tuna nets
  • 10.9.2 Patents excluded
    • 10.9.2.1 Excessive patenting and the decline of innovation
  • 10.9.3 Medicines for children
    • 10.9.3.1 Six-month extension
    • 10.9.3.2 Safeguarding against ‘double rewards'
    • 10.9.3.3 Access to data
    • 10.9.3.4 Funding for paediatric use of off-patent medicines

• 11.1 After the review
  • 11.1.1 Call for more aggressive incentives
    • 11.1.1.1 The Portuguese example
• 11.2 The impact of P&R
  • 11.2.1 Automatic reimbursement
  • 11.2.2 Degrees of switching
  • 11.2.3 Price linkage
• 11.3 Market conditions
  • 11.3.1 Generic pricing and reimbursement
  • 11.3.2 Patient co-payments
  • 11.3.3 Generic prescribing
  • 11.3.4 Generic substitution
  • 11.3.5 Marketing Authorisation
• 11.4 Sustaining generics medicines markets
  • 11.4.1 The need for demand-side measures
    • ..... The advantages of (relatively) free pricing
    • 11.4.1.1 Germany
    • 11.4.1.2 France
    • 11.4.1.3 Italy
  • 11.4.2 KUL recommendations for a competitive generic medicines market
  • ..... Introduce a coherent generic medicines policy
  • ..... Encourage price differentiation/competition within existing regulatory frameworks
  • ..... Disseminate pricing information to the relevant players
  • ..... Increase confidence in generic medicines
  • ..... Provide incentives for doctors to prescribe generic medicines
  • ..... Remove financial disincentives for pharmacists to dispense generic medicines
  • ..... Provide incentives for patients to demand generic medicines
• 11.5 Mixed messages for the generics industry
  • 11.5.1 The Portuguese campaign
  • 11.5.2 Denmark questions safety benefits
  • 11.5.3 Hungary: little interest in generic substitution
  • 11.5.4 Germany: opportunities squandered and health reforms
  • 11.5.5 AOK discounts criticised
    • ..... Stada to win
    • ..... A template for markets worldwide

• 12.1 A positive future for generics?
  • 12.1.1 Dispelling doctors' concerns
  • 12.1.2 Corporate optimism
  • 12.1.3 Remaining challenges
  • 12.1.4 A breakthrough on substitution

• Table 1.1 CDER New Drug Applications approved in calendar years 1990-2004 by therapeutic potential and chemical type
• Table 2.1 Generic- and cost-friendly provisions in the TRIPS Agreement
• Table 5.1 US patent expiries, 2007-2009
• Table 5.2 Health, education and defence spending as a share of US GDP, 1995-2005
• Table 7.1 Top ten US generic products by sales, 2004
• Table 8.1 Generic market shares in Europe by value and volume, 2006
• Table 8.2 Sales volumes for newly available generics in the four largest European markets, 2008-2012
• Table 10.1 Bolar implementation status in Europe as of February 2006
• Table 13.1 Blockbuster biotechnology products that faced patent expiry before 2007

• Figure 1.1 Price impact of switching to improved first-line combinations for HIV/AIDS
• Figure 5.1 Impact of consolidation in the US generics market
• Figure 5.2 Change in price of average generic drug prescription, 2002-2004
• Figure 5.3 Prescription drugs as a share of US healthcare spending, 1960-2005
• Figure 6.1 ANDA patent certification options
• Figure 6.2 Paragraph IV certification options
• Figure 7.1 Average annual sales of branded drugs losing patent protection, 2005-2009
• Figure 7.2 Dollar value of drugs losing patent protection in the US, 1995-2010
• Figure 9.1 How data exclusivity rules affect generic medicines
• Figure 11.1 Time delays for pricing and reimbursement approval in Europe after the granting of a Marketing Authorisation
• Figure 13.1 US pharmaceutical market by product type, 1999-2009
• Figure 14.1 Differentiating factors for hard-to-make generics