Regulatory strategies for small companies /SMEs



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TOPRA Module 1 Strategic planning in RA Regulatory strategies for small companies /SMEs A presentation by Ineke Jonker-Hoogerkamp, Director Regulatory Affairs Neurology, Genzyme Europe BV

Learning Outcomes EU - SME definition and legislation Implementation SME concept for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME funding SME partnerships / business development

In this presentation we will cover SME definition and legislation SME for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME partnerships / business development

EU legislation Commission Recommendation concerning the definition of micro, small and medium-sized enterprises (2003/361/EC 6 May 2003 into effect 1Jan 2005) Commission Recommendation covers all industries Annex contains definitions of: An enterprise Headcount and financial ceilings to define SME Types of enterprise Statistics on SMEs presented by Commission

SME : Micro-, Small- and Medium-sized Enterprise..are the engine of the European economy. They are an essential source of jobs, create entrepreneurial spirit and innovation in the EU and are thus crucial for fostering competitiveness and employment Aims at improved business environment for SMEs and promoting entrepreneurship, investments and growth. Günter Verheugen, Member of the European Commission, Responsible for Enterprise and Industry

Commission Recommendation An enterprise any entity engaged in an economic activity, irrespective of its legal form. This includes self-employed persons and family businesses engaged in craft or other activities, and partnerships or associations regularly engaged in an economic activity Types of enterprise Autonomous Partner Linked

Thresholds for SME Enterprise category Headcount: Annual Work Unit (AWU) Annual turnover or Annual balance sheet total Medium-sized < 250 < 50 million < 43 million or Small < 50 < 10 million or < 10 million Micro < 10 < 2 million or < 2 million

Commision Regulation European Commission booklet. The new SME Definition - User Guide and Model Declaration

Content SME definition and legislation SME for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME partnerships / business development

EMA - implementation SME concept EMA implementation Commission Regulation 2049/2005 adopted 15 Dec 2005 In order to reduce the costs for SMEs of marketing medicinal products authorised via the centralised procedure, that Regulation therefore foresees the adoption of specific provisions allowing a reduction of fees, deferring the payment of fees, and providing administrative assistance. Scope SME as defined in 2003/361/EC Covers human and veterinary medicinal products

EMA SME office SME office at EMA Dedicated to addressing the particular needs of smaller companies Advice to applicants Training and workshops User guide for micro, small and medium-sized enterprises Partnering and networking Newsletter

SME incentives Fee deferrals MAs and Inspections for MAs Fee reductions and exemptions Inspections (pre- and post-) : 90% Scientific Advice : 90% (non-orphan)/100% (orphan) Post-authorisation: 40% (small, medium)/100% (micro) Administrative and procedural assistance Waiver of MedDRA licensing (only for micro and small) Translations product information of MAA

EU legislation medicinal products How to get SME status? Apply to EMA Form Recent audited annual accounts Details of ownership Proof of establishment in EEA EMA review (~ 6 weeks) Issue EMA-SME number SME register

SME register Public SME Register > 1200 companies registered SME company profiles Company details Company sector (bio)pharmaceutical/med device and technology Product information / Product portfolio Product type Therapeutic area Product development stage

EMA Innovation Task Force (ITF) ITF mandate (06aug2014) internal EMA horizontal cross-sectorial group to focus in particular on Emerging Therapies and Technologies. brings together competences from various areas Quality, Safety, Efficacy, Pharmacovigilance, Scientific Advice, Orphan Drugs and GXPs, legal, regulatory affairs. Objectives ITF Establish a discussion platform for early dialogue with Applicants in particular SMEs to proactively identify scientific, legal and regulatory issues...

EU legislation medicinal products How to maintain SME status? Annual declaration of status + accounts No SME number = no benefits SME status easy ride with poor data

USA legislation medicinal products No SME status or overt benefits CDER's Small Business and Industry Assistance (SBIA) Program Office of Training and Communication Small business assistance bulletin Answer queries Orphan drug programme (grants/tax credits) PDUFA waivers/reductions in fees in some cases

Content SME definition and legislation SME for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME partnerships / business development

Regulatory strategy for SMEs Regulatory strategy depends on company profile and company goals Company stage as driver for regulatory strategy Early stage development - Science-driven regulatory strategy nonclinical up to proof of concept (phase IIA) Late stage development - Approval-driven regulatory strategy phase IIB clinical development up to MAA/NDA Marketed products - Market-driven regulatory strategy

Regulatory strategy for SMEs Regulatory intelligent development From registration to regulatory Regulatory intelligence tools Legislation Public regulatory documentation Science Comparators Nice to have versus Need to have

Regulatory strategy for SMEs SME in early stage development - Advice meetings with Agencies EU or national scientific advice Orphan drug protocol assistance US (pre-)ind meetings EU Paediatric plans.

Regulatory strategy for SMEs SME in late stage development products - submission and approval strategy Global or Regional strategy EU / US / Japan / MOW EU - Centralised/Decentralised/MRP EU - Conditional approval/exceptional circumstance US - Fast track/accelerated/priority review Orphan drug.

Regulatory strategy for SMEs SME in marketed products Maintenance Variations / Renewals / CBE30 / prior approval supplement Life cycle management Line extensions, Generics, Generics plus

Content SME definition and legislation SME for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME partnerships / business development

Comparison SME vs Big pharma Difference to Big pharma? NO - content Regulatory procedures the same except SME advantages Data package requirements the same YES - timing Big pharma driver - time to market SME driver - often financial resources

Regulatory strategy for SMEs Additional issues that interfere with regulatory strategy Cash position Time span financially covered Limited resources Milestone information stakeholders Stakeholders without pharma experience Pragmatic strategy vs. optimal strategy

Regulatory strategy for SMEs Need to have or less = Risk CMC development limited nr of batches, production of one small scale GMP batch stability, comparability Nonclinical development limited to essential studies for proof of concept late stage nonclin development Clinical development limited to a sub group, to certain regions market access

Regulatory strategy for SMEs Regulatory awareness Often low for SMEs and virtual companies However, need to be high especially for: Lean and mean dev strategy Changing strategy Soft skills

Content SME definition and legislation SME for medicinal products Regulatory strategy for SMEs SMEs compared to Big Pharma SME partnerships / business development

SME Funding Financing structure Private Venture Capital (VC) funded Partnership deals VC funded Investors want return on investment fixed amount of money time to cash out

Partnership deals / Business development Aim of partnerships Aimed at developing and implementing growth opportunities between multiple organizations The creation of long-term value for an organization from customers, markets, and relationships.

Partnership deals / Business development Partnership deals Licencing out Money in, Project gone Shared development Money in, Project stays, Lose control/ownership Work relationship with partner important Milestone driven Money in, Project stays until milestone Don t reach milestone - no money, no project

Business Development Process Find it, Get it, Create value Strategy Scouting & Screening Initial Evaluation & Due Diligence Negotiation & Contracting Integration & Alliance Management Source: Genzyme Corporation 33

Ways to Create Value Competencies Experience Track record of success Strong existing/prior partnerships Well-connected to experts Values Credibility Patient-focused heritage Biotechnology pioneer Well-recognized brands Resources Wherewithal Relevant technology (i.e. neurological models) Ability to dedicate staff Funding (cash or equity) Capabilities Complementary programs History of innovative regulatory achievements Reimbursement know-how Operational excellence Compatible goals/values Strong ethics Commitment Shared urgency Flexible, cooperative Transparent Reach Infrastructure in major markets Presence in relevant geographies Source: Genzyme Corporation

Value Creation is Paramount to a Good Partnership or Investment Source: Genzyme Corporation

In this presentation we have covered SME legislation EU and US SME requirements SME advantages to facilitate and increase chance of success Regulatory strategy for SMEs Difference to Big Pharma SME funding SME partnerships and business development

Take-home message SME regulatory and data requirements are the same SME status facilitates process and increases chance to success Regulatory strategy in SME often financially driven whereas time-driven for big pharma Challenge - align regulatory strategy with business goals

Recommended references Commission Recommendation 2003/361/EC 6 May 2003 http://eurlex.europa.eu/lexuriserv/lexuriserv.do?uri=oj:l: 2003:124:0036:0041:en:PDF The new SME Definition - User Guide and Model Declaration http://ec.europa.eu/enterprise/policies/sme/files/sme_defi nition/sme_user_guide_en.pdf Commission Regulation 2049/2005 http://ec.europa.eu/health/files/eudralex/vol- 1/reg_2005_2049/reg_2005_2049_en.pdf SME office user guide http://www.ema.europa.eu/docs/en_gb/document_library/ Regulatory_and_procedural_guideline/2009/10/WC5000041 34.pdf

QUESTIONS?

Acknowledgements Stacey Coen VP global business operations, Genzyme Corporation Contact details Name: Ineke Jonker-Hoogerkamp Tel: +31 35 699 1270 Email: ineke.jonker@genzyme.com