Regulatory Strategy for the Emerging Markets Far East, Africa, Middle East, Latin America

Transcription

1

2 Regulatory Strategy for the Emerging Markets Far East, Africa, Middle East, Latin America Alistair Davidson Senior Director, Global Regulatory Development, PPD

3 In this presentation we will cover Context and importance of Emerging Markets. Compare and contrast with ICH environment - outline of major regulatory procedures timelines and challenges How to build and execute successful strategies

4 Context and importance of Emerging Markets.

5 Global Pharma Industry Volume and Growth North America Size: US$ b Growth: -1-2 % Western Europe Size: US$ b Growth: 2-5 % Central & East Europe Size: US$ bn Growth: 8-11 % IMS Regional Pharmaceutical Outlook in 2012 (Global Market US$ 900 Billions /3-6% growth) Latin America Size: US$ bn Growth: % Middle East & Africa Size: US$ bn Growth: 5-8 % Asia Pacific Size: US$ bn Growth: %

6 Pharma market

7 Emerging Markets World population: 4.5% - USA 6.8% - EU 60% - Asia In the next 10 minutes: 77 children will be born in the US 100 children will be born in EU 1000 children will be born in India + China. 7

8 Diversity.. 8

9 and commonality PAY OUT OF POCKET VOLATILE LARGE POPULATIONS BRAND DRIVEN DYNAMIC WORKFORCES MULTICULTURAL FAST GROWING 9

10

11 Everything is possible in China. Nothing is easy. Patience is key to success. The answer yes is not necessarily an indication of agreement or confirmation. You don t understand China means disagreement. Provisional regulations mean the rules can change at any time even retroactively. Basically no problem means a BIG problem. Signing a contract means the beginning of the real negotiation. When you are optimistic, think about rule No. 2. When you are pessimistic, think about rule No

12 Compare and contrast with ICH environment - outline of major regulatory procedures timelines and challenges

13 ICH/ICH-aligned countries: common characteristics Adoption of ICH guidelines Independent review Information sharing Harmonisation Strong IPR and regulatory framework Transparent and accountable authorities Priority review Rx-OTC separation R&D facilitated

14 Considerations for Regulatory Strategic Development in Emerging Markets Regulatory requirements Clinical Development File format and content Label Source CPP Samples Clinical trials Life cycle TIMINGS Other considerations Medical practice/epidemiology Medical/commercial need Cost/logistics Intellectual Property Protection Capacity and capability Local/generic vs R&D/MNC Language and culture Caution/suspicion TIMINGS

15 The Emerging Markets Regulatory Challenge Across a wide number of countries and internal/external systems: Drive consistency of approach (efficiency/compliance) While Giving top quality support to key business drivers Very BROAD range of reqts/systems across many countries DEEPENING technical, clinical, regulatory expertise in key countries

16 Challenges at Agency Level Getting smarter Access to more info than ever before Resources generally not keeping up Under HIGH pressure Flexible: good & bad Reliance on others Focus on initial approval life cycle capabilities generally not well-developed

17 USA FDA cf China SFDA USA - FDA Around total employees 400 pharma companies, 300 biotech companies Excellent infrastructure, Progressive, innovative, transparent, accountable PDUFA - set standards for review timelines IND review fast China - SFDA Staff strength: 180 at SFDA (19 for registration and administration); 120 in CDE for drug review), 400 at the different centres working for SFDA and 1500 in 30 provinces Approx 5000 pharma manufacturers, including biotech companies 6294 applications received in 2010; 61.7% are generics Need to improve technical knowledge and better understand international review practices (FDA/EMEA)

18 Local Clinical Data Requirements Country Local Clinical data requirements China Phase I and Phase III (at least 100 patients each arm is part of global trial) S. Korea Phase III in Korean patients if not qualified for bridging waiver Taiwan Could accept other Asian data. Local study is bridging study evaluation failed Vietnam Data in local patients required. Lifted 5 years after approval in reference country India Local study with pivotal design. Could be qualified for waiver in case of unmet medical need Mexico Mexican patients in phase III Russia Russian patients in phase III or local trial. Local BE study for generics is required.

19 Foreign Clinical Data in US Applications 30% of Phase III trials in 2007 conducted outside of US (157 of 509) More than 50% of the study sites outside of US (13,521 of 24,206) From 1995 to 2005, the number of countries serving as trial sites outside the US more than doubled

20 Regulatory Requirements: N. Asia China/Japan/Korea/Taiwan: require a level of local (or Asian) supporting data CHINA: Most common registration route is Class III registration chemical drugs Phase I PK data in Chinese patients Phase III data in at least 100 Chinese patients per arm for global clinical trials JAPAN: Full Japanese bridging clinical development (Phase I-III) required, per ICH E5 PMDA will accept Asian data provided significant number of Japanese patients KOREA: Require local bridging data to global clinical data package, per ICH E5 Phase III Safety/efficacy data in Korean patients and no official patient numbers stated TAIWAN: Require bridging data to global clinical data package, per ICH E5 No minimum patient numbers stated, but flexible in accepting Asian, non-local Phase III data Incentives in terms of speed, help with study and reimbursement outcome 20

21 International, Multi-center Trials SFDA Data The participation degree of China in the synchronic research of global new drug research and development is increasing year by year. In total, 320 clinical trials from foreign applicants that were approved in 2009, 132 are international, multi-center clinical trials, significantly increasing compared with last years. Zhang Wei, Dept of Drug Registration, SFDA,

22 Current Future Clinical Development Map? Future Use data gathered in US/EU to justify registration in Asia Use data gathered in Asia to justify registration in US/EU

23 WHO Certification Scheme Certification confirms that certifying Authority has evaluated an application and approved it on the basis of the quality, safety and efficacy (QSE) Therefore CPP from any (competent) issuing Authority provides same reassurance Irrespective of source country marketing status Ref: EFPIA/IFPMA position

24 The file.. CTD? CTD plus? CTD minus? ACTD? International file? Country specific file? OTHER What is sent from HQ vs What is submitted vs What is reviewed vs What is Approved Impacts label Impacts life cycle strategies Impacts renewal/re-regn Impacts COMPLIANCE

25 Manufacturing strategy CPP/LABEL SAMPLES What? When? Numbers? TIMELINES LIFE CYCLE PRICE

26 China - Regulatory Environment, no longer just a Great Wall Has always been considered complex Long lead times compared to others Difficult to predict review outcomes Requires IND and NDA reviews and sample testing Overload in period with drug application up to 20,000 cases annually , approx 6,000 applications annually. But Becoming much more professional; re-organisation SFDA and CDE Access to more resources; formal/informal links to other agencies Development of new specific regulations and guidances, eg. Special review Publishing targets and results Globalising: e.g. participating in APEC; Tripartite forum (China, Japan, Korea), ICH GCG PIC/S: Pharmaceutical Inspectorate Cooperation Scheme (e) CTD: electronic Common Technical Document GRP: Good Regulatory/Review Practice DMF: Drug Master File

27 Harmonisation? GCC

28 Present/Future: Global Development Regulatory Programme Pre-submission, submission and Q&A activities in narrower time-windows: concentrated global effort required Approvals in a Narrower Time Window Pre-registration Activities SUBMIT Q&A APPROVE U.S. SUBMIT EUROPE Q&A APPROVE SUBMIT Q&A INTERNATIONAL 100+ APPROVE 28

29 How to build and execute successful strategies

30 At the Starting Line USA and EU regulatory strategies Commercial priority globally and regionally Global development plan and timelines Key emerging countries Competition Manufacturing strategy Any 3 rd party commitments Resources to deliver Plan B, C..

31 Four Pillars for Operational Success ALIGNMENT Mutual understanding HQ Region Country [agency] Clarity on roles and responsibilities Senior management awareness, planning and reporting Key stakeholders internally in manufacturing, labelling etc. If using a 3rd party ensure no less clarity there PEOPLE Hiring, training, coaching, retention. Differentiating roles: leader, strategist, writer, compiler, publisher, expert INTELLIGENCE Capture, harness, interpret and exploit. Map the future and use that intelligence as influencing lever. PROCESSES Routine where at all possible. Appropriate standard while achieving compliance. Simple limited KPIs/measures.

32 Alignment Business Plan Business Plan Business Plan Business Plan Regulatory Mgt/Ops Regulatory Mgt/Ops Regulatory Mgt/Ops Regulatory Mgt/Ops Regulatory Options Regulatory Options Regulatory Options Regulatory Options Agency Agency Agency Agency Agency Program Execution Business Plan Business Plan Business Plan Regulatory Mgt/Ops Regulatory Mgt/Ops Regulatory Mgt/Ops Regulatory Options Regulatory Options Regulatory Options Agency Agency Agency Agency Agency Program Plan Execution

33 Key Timeline Factors: Regulatory support to clinical development Process EC process MoH process o Interdependencies of above Import licence Site identifciation and preparedness Validity period of Clincial trial certificate Rate limiting steps Agreement on strategy and plan: o Countries/numbers of patients o Protocol o Sites Agreements/contracts with sites, inc budget Availability of documentation Understanding of need for and timing of various documentations Translations o Multi-language o Authority/Ethics documents vs documents for patients

34 Balanced Country Selection Ensure future data integrity by combining countries without major ethnic differences and defining needs for recruitment caps Separate study for countries with contradicting guidelines or agency advice Measure impact on global development when include countries with long study start up Account for requirements to supply study medication and/or concomitant therapy after completion of the study

35 People Profile Committed to Quality Business oriented Process-minded Need re-fillable pool Central/virtual location for global support: offshore/outsource? Cost-effective Effective and fast on-boarding/training Opportunities for growth and development

36 People PLANNING Build and manage work plans master and detail Able to tailor plan to match internal resources and stakeholder expectations Need to proactively manage peaks and troughs Ensure easy access to plans by all concerned in multiple formats (by project, by country, by reg exec etc) QUALITY Overall drive for the Quality value throughout function Co-ordination of efforts on optimising Quality Involvement in relevant audits/inspections Ensure implementation and sharing of lessons learned Oversees any 3rd party outsourcings to ensure seamlessness and consistency in QUALITY value Ability to work inside a bigger group; capable of working with all levels within that group routinely

37 Intelligence PEOPLE Local experts globally Understanding and application of official requirements How it really works. Central strategic expertise Building strategies and plans across territories and programs Exploiting synergies/links/bundling opportunities Adjusting from experience Planning for What if. SYSTEMS Dedicated capture of requirements, processes, timelines Ensure accurate, up-to-date Regulatory information Diligent monitoring, gathering, interpreting and communicating Single source knowledge base for all regulatory information

38 Processes Robust IT tracking/reporting system, able to meet all clients needs SOPs/WIs etc: simple, intuitive, appropriate to output, defendable Over time, build on intelligence/experience to offer better results in respect of time, quality, efficiencies Strong governance and self-auditing function Processes work for the function and the output, not vice-versa

39 How long..? From when to when? Varies by country Varies by application type Often varies by product/applicant Use most recent experience Use reliable metrics to benchmark Regular checks at country level

40 Key: relationship and communication between HQ team and local team TEAM All players to know and understand roles Start early Regular updates Handle on global situation Communicate with and USE Clinical and Commercial throughout strategy-building and execution Publicise the successes look for replications elsewhere Learn from failures Strategy: managing within

41 Concluding Key Regulatory Success Factors Local RA team/manager owns authority relationship and requirements Good relationships critical Internal RA: central local external Supplier Regulatory Authority Key functional partners: commercial, clinical, legal, BD Regular communication Build and store goodwill, someday you will need it ((internal and external) Business plans WILL change at short notice Proactively add value to business Not you can t You can Own and solve regulatory resource issues Internal re-allocations Outsourcing/off shoring Integrity, openness, transparency 41

42 Review In this presentation we have covered: Context of importance of Emerging Markets. Compare and contrast with ICH environment. Outline of major regulatory procedures, timelines and challenges; how to build and execute successful strategies

43 QUESTIONS

44