4Current EU GDP Regulations EU Guidance on Wholesale Distribution Practice (94/C 63/03)Sell to retail pharmacies without alteration of product propertiesQuality System should ensure:AuthorisedStorage conditions observed (incl transport)No contaminationStock turnoverStored safe and secureRight product, right address, satisfactory time periodTracing system to allow recall
5Key Elements in Regulations Responsible person (oversee Quality System)Written contract with RPWritten proceduresChecking Bona Fides of suppliers and customersStaff TrainingRecords/traceabilityEmergency plansCounterfeit Medicines
6US Guidance on Distribution Not explicitly in 21 CFR 210/211USP <1079> often regarded as FDA benchmarkOther GuidanceUSP <1083>The Food and Drug Administration Safety and Innovation Act (FDASIA)US Senate Health, Education, Labor & Pensions (HELP) Committee consultation of Track & Trace
7Distribution in a Nutshell Storage & TransportationE2E Supply Chain
9The Supply Chain Fragments…. Prevailing business model vertical integrationlocal market management presence.predominately small molecule manufactured by chemical synthesis.1980’sOutsource non-core activitiesManufacture, analytics, distribution, storageSinceNew business models - innovator, virtual, biotech, generic/bio-similars and speciality PharmaBiologics form important portfolio position, with temperature and time sensitivitiesMarkets have globalised into new territoriesNumber and location of third party contractors and service providers proliferate.
10Dis-integration of the supply chain Outsourcing begins in earnest…..
11Integrity issues…Economically motivated adulteration – “Heparin, supplied by Baxter, found to be adulterated, with reports of 574 adverse events and nine patient deaths estimatedJ&J/McNeil placed under a ‘Consent Decree’ after recalls associated with supply chain issues.Novartis shells out hundreds of millions $ in manufacturing issuesShortages in US/EU supply chains result in governments and general public questions.
12Security issues…..“Abbott hit by $4m diagnostics theft in USA” (June 2011)“Eli Lilly warehouse thieves make off with $76m haul” (March 2011)Counterfeiting – “Operation Singapore, 2 million doses of counterfeit medicine enter UK supply chain in 2006/7”.“FDA is still concerned that the drug supply is increasingly vulnerable to diversion of legitimate drugs (ie stolen or sold illegally)”. Rx-360 Newsletter September
13The fall-out….Crippling impacts in the areas of patient safety, brand image and reputation, costs of remediation, customer service and investor confidence.A UNIVERSAL CRY FOR CHANGE!From regulators, governments, other competent authorities and patient advocacy groups.
14What has been the response? …EU implements Falsified Medicines Directive.…EMA consults on dramatic tightening of GDP/GMP…FDA pens “Pathway to Global Safety and Quality”.…US Congressional Committees investigate.…President Obama wades in on drug shortages.…US Pharmacopeia consults on new Chapter < 1083 >.…PEW Charitable Trust writes report “After Heparin”.…GS1 Global Traceability Standard for Healthcare (GTSH).
16Regulators collaborating globally FDA joins Pharmaceutical Inspection Co-operation Scheme (PIC/S).FDAs “Pathway to Global Safety and Quality” for systems to collect and share data between competent authorities across the world.The Food and Drug Administration Safety and Innovation Act (FDASIA), Title VII
17Directive: Falsified Medicinal Products 2011/62/EU SCOPEExtending regulation to brokers of medicinesStrengthened obligations on wholesale dealersImproving controls on quality of active substances and certain excipientsRegulating medicines imported for re-export – new term “introduced” and rules governing access to medicines held in free trade zones & warehousesRequiring safety features for medicines at risk of counterfeitingAddressing the internet supply of medicinesStrengthening inspection and ensuring appropriate penalties for counterfeiting are in place in Member States
18Revised Guidelines on GDP - Consultation Quality Management (Ch 1)Senior management commitmentManagement of outsourced activitiesRisk managementPersonnel (Ch 2)Responsible PersonOrganisation chartTraining in GDPOperations (Ch 5)Marketing Authorisation Holder (MAH) informedQualification of suppliers and customers
19Revised Guidelines on GDP (cont’d) Suspected falsified medicines (Ch 6)Distributors must inform competent authority and MAH immediately – procedure defined.Contract Operations (Ch 7)Written agreement allocating responsibilitiesTransportation (Ch 9)Delivery drivers trained in GDPMaximum limit of 24 hours for transport hubsWholesalers distribution authorisationSpecific provisions for Brokers (Ch 10)Register and have quality management system
20GMP/GDP Regulations tightening Traceability to be reflected in Chapter 5 of GMP Guidelines, which will require “A record of where each active substance (including its critical starting materials) is manufactured, propagated, processed and handled prior to its use in the manufacture of a medicinal product.Tightening of requirements to check ‘Bona Fides’ of supply sources and other trading partners.Safety features required for products at risk of counterfeiting (eg. serialisation/authentication).
21Regulations tightening (continued) Quality/Technical Agreements required between all actors in the supply chain with the Marketing Authorisation Holder (MAH) shouldering more responsibility.More stringent control in storage whereby some actor/logistics providers, holding product for greater that 24 hours, may require a Wholesale Dealer Licence (WL).A New guidance from EMA on GDP for active substances.
22Barriers to traceability Links between MAHs and DistributorsBrokers/Agents/IntermediariesDocumentation eg C of ACommercial secrecyDrug Master Files (DMFs)Scope of Technical Agreements/ContractsComplex and expensive technology optionsOwnership of the process of change
23Improvement Opportunities Quality/Technical Agreements defining mutual engagement processes, not tick boxes.Well defined processes for product and material procurement .Properly negotiated supply agreements that include risk sharing and performance criteria.Ownership amongst CMOs and DistributorsDirection from sponsor companies (esp virtual)Proper briefing and requirements specs for 3PLs.Application of risk-based approaches to target resources at critical areas.
24What is the long-term solution? Integrate strategically upstream and downstreamBuild shared processes and practices with business partnersAim to look at principles behind the regulations and manage riskKeep an end-to-end perspective on the supply chain at all times
25Useful linksEU GDP Consultation: Responses to EU GDP Consultation: EU Good Manufacturing Practice Directive (2003/94/EC): EU Good Distribution Practice Directive (94/C 63/03): EU GMP/GDP: DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT Supply Chain Management in the Drug Industry: Delivering Patient Value for Pharmaceuticals and Biologics, J Wiley & Sons, NJ, February
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