Generic substitution and licensing PDIG Summer Symposium

10 June 2010

Generic substitution

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What’s a generic medicine?

Legally “‘generic medicinal product’ 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. [...]” [Art 10.2(b),Directive 2001/83/EC, as amended] Practically The same active ingredient as the original branded product The same effect on the patient Demonstrated by appropriate scientific studies Licensed by the same regulators … … to the same standards of safety quality and efficacy as the original branded product 3

Definitions

Generic substitution Bioequivalence Interchangeability •An administrative process whereby a dispenser may fill a prescription written by brand with an equivalent generic medicine •A regulatory process by which a generic medicine is demonstrated to have the same effect on the patient as the reference (branded) medicine •The ability to switch patients between different manufacturers’ versions of the same medicine without difference in therapeutic outcome—a function of bioequivalence Health warning •Many commentators use these terms interchangeably and thus confuse the issue 4

National comparisons

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Benefits of generic medicines

Affordability Innovation Security of supply Reduction in the NHS drugs bill allows the NHS to pay for the cost of new innovative medicines that patients need: financial headroom for innovation Initial market monopoly for brands incentivises innovators by allowing them to make a return on their R&D investment Generic competition encourages innovation: otherwise, innovators would be able to rely on their old products for commercial success Multiple suppliers of generics increases the security of supply of medicines to patients by minimising the impact of production difficulties At patent expiry generic competition reduces the NHS drugs bill, making it affordable (without generic competition, the drugs bill would double) 6

Life cycle relationship with original brands

Generic competition Brand monopoly

Development of original brand Launch of original brand Effective patent / SPC protection of original brand * Launch of subsequent generics Average brand cost = £20.00

Average generic cost = £3.83

NHS saving due to generic competition = £8.6bn per year for England Brand Development of generics Launch of first generic Generic * Includes patent, patent extension, data exclusivity, paediatric exclusivity, etc 7

Substitution consultation

Consultation provided for in the PPRS 2009 • Not asked for by the generic industry Three options proposed by DH • Do nothing • Dispensing flexibility with specific exclusions of a selected group of products • Dispensing flexibility applying only to a selected group of products Prescribers to be able to “tick in” or “tick out” DH preferred Option 3 • With prescribers’ ability to tick out 8

Issues raised Safety

• Generics are approved by the same regulators to the same standards of safety quality and efficacy as the original brand

Bioequivalence

• Originators use bioequivalence studies too • Number of subjects in the test varies according to the variability of the active ingredient • Narrow therapeutic index products are assessed against a range of 90 – 111% variation c/f 80 – 125% for normal products • Range reconfirmed following two year review by European regulatory authorities • Bioequivalence testing avoids unnecessary testing on humans and animals 9

Issues raised

Variability & interchangeability •All medicines have inherent variability •Variability of generics often less than original brands because they are developed after 20 years of scientific advance •The MHRA has not withdrawn any generic due to concerns about interchangeability •The MHRA requires non-interchangeable generics to have a brand name Innovation •Generic competition incentives innovation •Generic manufacturers undertake incremental innovation Security of supply •Multi-source generics suffer fewer shortages than single-source brands Pharmacy position •Cautious •Sought greater autonomy and input 10

BGMA position

Supports DH proposals •Consistent with the principles which underpin cost effective medicines use in the NHS Supports Option 3 •Positive list of products to which substitution will apply •“Tick out” option for prescribers Products should be described by rINN •Salts should not be separately referenced as are legally and scientifically equivalent Agree criteria for listing •Only products listed in Part VIII of the Drug Tariff should be listed •Interchangeability should be judged scientifically by the MHRA •More products should be listed 11

BGMA principles

The prescriber should be responsible for deciding which medicine a patient receives, but not its manufacturer • Competition in the off-patent market drives down prices and increases access to medicines by reducing the drugs bill • The greater the use of generics, the less money the NHS spends The use of INN prescribing is the most convenient way to ensure cost-effective use of medicines through maximum use of generics 12

Generic licensing

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Abridged procedure

Results of pre-clinical tests and clinical trials not required if the applicant can show that the product is a generic of the originator product which has been on the market for 8 years Generic medicine not to be placed on the market for 10 years following the initial authorisation of the reference product 10 year exclusivity period to be extended to a maximum of 11 years if the originator obtains during the first 8 years an authorisation for one or more new therapeutic indications which offers significant clinical benefit 14

Abridged procedure

Research & development • EU guidelines • Bioequivalence – guideline updated 2010 • Product development identical standards to innovator with benefits of technical advance 18 – 24 months Dossier SmPC and PIL/Label Clinical & Toxicology.

Refer to innovator, not repeated Bioequivalence Clinical link Chemistry and Pharmacy • Drug Substance • Drug Product Assessment to current EU standards 1. Validation 2. First Assessment (medic, pharmacist, toxicologist, statistican) 3. Questions to company 4. Answers to MHRA 5. Q+A repeated until MHRA satisfied 6. Marketing Authorisation Granted 18 months Launch at patent off 15

Reasons for different indications Differences in reference product

• Based on national approvals with different indications • Generic company may take lowest common denominator

Use patents / data exclusivity

• Drug substance may lose exclusivity • Some indications may still be protected • Generic manufacturer demonstrates full bioequivalence • But removes protected indication from SPC and / or PIL 16

Impact

Response in the supply chain • Manufacturers do not promote “off label” • Healthcare professionals act according to legal and professional requirements and their professional judgment Off label prescribing • Not an “unlicensed medicine” • Satisfied by evidence base • Explain why not indicated • Accurate records Dispensing • Required to dispense what’s prescribed • No legal prohibition of off label dispensing • Pharmacist may revert to prescriber 17

Thank you … … And questions

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Members and Contact

Warwick Smith Director-General British Generic Manufacturers Association The Registry Royal Mint Court London EC3N 4QN T: +44 20 7457 2065 M: +44 7974 565 424 E: [email protected]

W: www.britishgenerics.co.uk

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