1. © Safeguarding public health Expert Group on Innovation in the Regulation of Healthcare products Adaptive Licencing workshop at the Wellcome Trust October 15, 2012

2. Slide 2 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Expert Group work programme Early Access work International/comparative experience Clinical trial activity in the UK Defining the challenge in regulatory innovation -including Adaptive Licensing and developments in PV Mapping projects and initiatives -UK and US (Newdigs) Related initiatives -Advanced manufacturing regulation

3. Slide 3 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Developments and Action Information on flexibilities in existing licensing routes -On internet and with representative bodies -MHRA Paper Early access consultation EU proposal on Clinical Trials -Wide range of other work under the Growth Review Adaptive licensing -Initiatives and thinking on adaptive licensing -Key questions and scoping -A pilot programme of activity on adaptive licensing by Dec 2012

4. © Safeguarding public health Early Access

5. Slide 5 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Early Access Scope of the scheme -New medicines in areas of unmet need -Benefit:risk profile of the medicine must be positive -Availability restricted to predefined patient population Characteristics of the scheme -MHRA provides scientific opinion on the medicine -Medicine could be available for around 1 yr before licence granted The medicine remains unlicensed -No advertising permitted

6. Slide 6 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Early Access Eligible patients -Patients of any age (including children), no CT participants Eligible drugs -Restricted to any therapeutic area with un-met need Safety monitoring requirements -ADR reporting requirements will apply, additional monitoring tbd on a case by case basis

7. Slide 7 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Early Access Pricing -Freedom of pricing for producers of EA drugs but -NHS Trusts decide on purchase of medicine (lower cost encourages NHS uptake) Patient consent and liability issues -‘Active’ patient consent -Effective information dissemination -Manufacturer remains liable for supplying defective product Additional criteria -Benefit to UK economy -NHS funding for the medicines must be cost effective

8. © Safeguarding public health Adaptive Licencing

9. Slide 9 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Adaptive Licencing: EU / UK? Existing Legislation or not? If a UK scheme -Unlicensed use under the professional/legal responsibility of prescriber -Product for un-met need -Essentially a variant of Early Access If EU scheme -Centralised product; EU regulation applies -EMA, not UK coordinates licencing decision -European Commission will be the licensing authority Existing regulation or not? -Essentially a matter of time-frame

10. Slide 10 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Adaptive Licencing 3 levels of activity / tripartite structure -Level 1: EU (EMA, CHMP discussions) -Level 2: HMG/MHRA -Level 3: Industry / third sector Critical role for EU -EU licensing process -European Commission will be the licensing authority Considerable opportunities for action under current rules -Alternative means long timeframes Industry must come up with a product/asset -None identified so far – on either side of the Atlantic Merit in both retrospective and prospective work

11. Slide 11 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Adaptive Licencing Critical issues in regulatory decision making (risk/benefit calculation) -Evidential levels to apply -Role of RCTs – and use and interpretation of observational data Industry policy / public health policy -Industry financial/business risks / interests? Patient / professional / media understanding Wider system challenges: -Pricing / VBP -Company decisions / management of their development pipelines and processes Pilot project by end 2012

12. Slide 12 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © An “asset” or a product Likely characteristics: -break/-through product for as yet un-met need -Perhaps not as “open and shut” as Glivec, but not far off -Likely to be for small(er) patient population ·but not necessarily -For some of the AL ideas, possibly a product with multiple potential uses -[Probably] something with an identified patient group ·Informed consent etc

13. Slide 13 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Adaptive Licencing - Forward Look EU / EMA -Management Board discussion: March 2013 -CHMP and other EMA committees -Commission HMG/MHRA -Defining the pilot, and the problem(s) it is to solve -Licensing routes available -Toolbox of options -Structures and roles -Governance framework needed -Relation and link with industry/third sector support project

14. © Safeguarding public health Conclusions of Expert Group meeting October 9 2012: focused on Adaptive Licensing

15. Slide 15 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Conclusions of EG meeting, Oct 9 AL to be positioned at EU level within current legislative framework Tripartite project structure makes sense Practical programme of activity by the end of the year Need to be clear about what questions we are trying to solve Regulation, Clinical Trials, purchasing and R&D strategies within companies all relevant

16. Slide 16 Oct 15, 2012 Adaptive Licencing Workshop at the Wellcome Trust © Work and steps ahead Commissioned papers: -Pharmacovigilance Further consideration: -EMA level work on regulatory challenge of AL -Capacity of CPRD wrt AL Pilot project for the end of the year -Retrospective and prospective activity -Identification of potential products