New Dynamics and Challenges in the Generics Market 2007

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