Challenges and Keys to Success for an Orphan Drug Product Launch. Evelyn Kelly MPharm MPSI MBS

Transcription

1 Challenges and Keys to Success for an Orphan Drug Product Launch Evelyn Kelly MPharm MPSI MBS

2 Orphan Drugs Rare Disease definition: any disease or condition that affects fewer than: US: 6 per 10,000 people Japan: 4 per 10,000 people EU: 5 per 10,000 people Less than 5% of rare diseases have a treatment Orphan Drug: pharmaceutical product that has been developed specifically to treat a rare medical condition Special incentives introduced by governments to stimulate markets: US: Orphan Drug Act 1983 (7 + years of exclusivity, 50% tax credit on R&D costs, grants, waiving of user fees, expedited approval etc.) Japan: 1993 EU: 2000 (10 years exclusivity) Pre 1983: 38 orphan drugs approved in US. Since 1983: Over 600 drugs/biologics developed and marketed for rare disease in US.

3 Pre-submission considerations for Orphan Drugs. Decision on business model/office location Manufacturers are your partners, not your suppliers Named on MA, legally responsible for key activities Decision on business model/office location Can leverage European MA experience when submitting MA in other regions e.g. Australia, Brazil etc. Decision on type of Marketing Authorisation & who holds MA Supply Considerations on MA Content e.g. temperature parameters, shelf life etc. Selection of Manufacturers to support MA submission in outsourced model Decision on what to retain and what to outsource e.g. QP release Impact of MA decisions on submissions in other regions. Centralised authorisation typical choice but consider all authorisation options to get optimum one for your business model Very Important!! How often are Supply Chain colleagues involved in this??? Consider outsourcing initially then bring activities in house once entity & team established 3

4 Entity Set Up..Considerations Will office own Marketing Authorization? EU Office? (Switzerland) Financial, tax & legal implications of office location Licenses required by office WDA, MA etc. Office facilities, temporary office location considerations Address on pack Customs Considerations Brexit Availability of local talent, location of various functions

5 Orphan Drugs Virtual ROW Supply International Office (based in Ireland) Virtual product flow from Ireland/ Europe to customers Revenue recognised in local entity Alignment of regulatory/tax/legal/ customs & finance requirements Demonstrate that activities are managed/channelled through Office Alignment of physical and virtual legislative requirements critical

6 Orphan Drugs: Physical supply considerations. Physical Flow (from selected Distribution partner): Consignment stock (risk) Global (temperature controlled) shipments Support services e.g. Customer service, transport, account management, QA Alignment of tax/legal requirements with physical storage Patient Distributor/Wholesaler (MA Holder?) Hospital Multiple delivery requirements depending on region/country Pharmacy Local entity

7 Launch Process Identify Business Opportunity List of Potential Partners Conduct Partner Due Diligence Endorsement of opportunity/partner Determine Route to Market Partner Qualifications/Set Up Agreements Commercial? EAP? Marketing Authorization? Local release/license requirements Packaging/Artwork requirements Customs requirements PV requirements Distribution Channel Order Management Logistics & Transports Documentation Tax Customer Approval Invoicing and Finances Order Received/ Shipped/Delivered Ongoing supply/ Planning & Forecasting

8 Compliance Considerations Regulatory /Route to Market Set up local entity or go direct? (EU) Commercial or EAP sale? Reimbursement method? EU: Centralised license v s local requirements Who is MA holder? Can PTC be holder locally? Additional local licenses/poa required? Temperature requirements ambient, cold chain Specific product requirements e.g. gelatin free etc. Mandated pack size? Formulation of product? Samples/Ancillaries required? Customs Broker support required? Documentation required e.g. pro forma invoice etc. Values and details required on documentation Import permit required? Common issues which can delay item in customs Origin of product determination & certificates Duties to be imposed and where does liability lie Incoterms Quality Assurance/PV License requirements e.g. manufacturing, wholesaler, controlled substance EU Importation & Market Release- Qualified Person Regional/local release requirements Regional/local testing and sample retention requirements Documentation requirements e.g. CoA, CoC per delivery/ batch Assessment and qualification of local vendors: audits, agreements Bonefides/Returns/Recalls/Investigations Adverse event monitoring Legal/Tax Office/legal entity requirements Contract and confidentiality requirements Intellectual property Due Diligence Vat requirements and exemptions Intrastat reporting Applicable taxes chargeable where? Local entity required?

9 Supply Chain Considerations Packaging Pack/PIL requirements? Requirements for local approval/release e.g. sample packaging etc. Blue box/braille requirements Pack count - mandated EAN/Barcode requirements e.g. 3D Local language requirements/translation Local artwork requirements e.g. colours/fonts etc. PIL: Local PV/Website/distributor details required Serialisation requirements Local labelling e.g. Bollini etc. Logistics/Shipping Selection of optimum transport provider Transit time to market Transport method road, air Transport container e.g. shipper, dedicated truck, pallet Temperature monitoring/control Documentation requirements Weight, dimensions Packing and handling of product cytotoxic, fragile Planning/Forecasting/inventory Confirmed forecast/patient count for market Production planning and co-ordination Agreed production timelines with CMO Production capacity available Tracking of Inventory - electronic interface (SAP) or manual reports Local inventory data how will this be provided Analysis of Inventory trends to support forecasting Sales & Operational Planning Customer Service/Order Processing Order form and process establishment Training and query management Customer and country set up Customer approval and bonefide check support Receipt of PO and confirmation of delivery timelines Invoicing for multiple markets Multilingual service Quick response and availability

10 Finance Considerations Local entity or channel finances through International entity Tipping point for model change Consignment/purchased stock and change of title point Tax requirements Cash Collection and bank reconciliation Set and approve pricing structures (including discount/foc product) Payment terms and conditions Customer credit checks Debtor management Reports required from local partners/distribution partner Pre payment markets pro forma invoices and tracking of payments Payment of local accounts Currency considerations 10

11 Local Partners to support Launch Key Requirements Contract QTA/PV agreements Legal due diligence, IP etc. Scope of work they will complete e.g. MA holder, 3PL only, local customisation of packs, marketing and sales support etc. Territory covered Facilities and licenses Processes vendor uses and support functions Local knowledge Account/project management Experience in aligning multiple requirements Experience with virtual supply model/orphan Drugs Consignment or purchased stock Competitive pricing 11

12 General Points Double check that requirements are applicable to Orphan Drugs special exemptions in place for these low volume, high value drugs Re-check knowledge each time you enter a market changes to legislation Challenge any points that seem unusual or difficult to comply with Challenge timelines to ensure they are realistic Try to ensure that interpretation of requirements is advised on locally (especially supply path considerations) Incorporate buffers into time estimations to complete activities Consider cross functional impact to ALL decisions even basic stock movements can have VAT/Finance implications Establish expert internal cross functional team Build International consultancy/industry network 12

13 General Points Establish processes early to minimise firefighting - beware of agreeing to exceptions for one market! Align activities with local Commercial objectives and timelines establish Sales & Operational planning early Understand budget, contract and approval constraints both internally and for local partner Keep focused on patient s need to receive product 13

14 Thank You! 14