1. Good Distribution Practices: What do they mean to you?
Presented by: Hedley Rees, Biotech PharmaFlow, UK

2. Agenda Distribution in Pharmaceuticals
Why has GDP become such a hot topic?
What is the current global landscape?
What are the issues and opportunities?
Q&A session

3. Distribution in Pharmaceuticals

4. Current EU GDP Regulations
EU Guidance on Wholesale Distribution Practice (94/C 63/03)
Sell to retail pharmacies without alteration of product properties
Quality System should ensure:
Authorised
Storage conditions observed (incl transport)
No contamination
Stock turnover
Stored safe and secure
Right product, right address, satisfactory time period
Tracing system to allow recall

5. Key Elements in Regulations
Responsible person (oversee Quality System)
Written contract with RP
Written procedures
Checking Bona Fides of suppliers and customers
Staff Training
Records/traceability
Emergency plans
Counterfeit Medicines

6. US Guidance on Distribution
Not explicitly in 21 CFR 210/211
USP <1079> often regarded as FDA benchmark
Other Guidance
USP <1083>
The Food and Drug Administration Safety and Innovation Act (FDASIA)
US Senate Health, Education, Labor & Pensions (HELP) Committee consultation of Track & Trace

7. Distribution in a Nutshell
Storage & Transportation
E2E Supply Chain

8. Why has GDP become such a hot topic?

9. The Supply Chain Fragments….
Prevailing business model vertical integration
local market management presence.
predominately small molecule manufactured by chemical synthesis.
1980’s
Outsource non-core activities
Manufacture, analytics, distribution, storage
Since
New business models - innovator, virtual, biotech, generic/bio-similars and speciality Pharma
Biologics form important portfolio position, with temperature and time sensitivities
Markets have globalised into new territories
Number and location of third party contractors and service providers proliferate.

10. Dis-integration of the supply chain
Outsourcing begins in earnest…..

11. Integrity issues…
Economically motivated adulteration – “Heparin, supplied by Baxter, found to be adulterated, with reports of 574 adverse events and nine patient deaths estimated
J&J/McNeil placed under a ‘Consent Decree’ after recalls associated with supply chain issues.
Novartis shells out hundreds of millions $ in manufacturing issues
Shortages in US/EU supply chains result in governments and general public questions.

12. Security 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

13. The 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.

14. What 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).

15. What is the current global landscape?

16. Regulators 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

17. Directive: Falsified Medicinal Products 2011/62/EU
SCOPE
Extending regulation to brokers of medicines
Strengthened obligations on wholesale dealers
Improving controls on quality of active substances and certain excipients
Regulating medicines imported for re-export – new term “introduced” and rules governing access to medicines held in free trade zones & warehouses
Requiring safety features for medicines at risk of counterfeiting
Addressing the internet supply of medicines
Strengthening inspection and ensuring appropriate penalties for counterfeiting are in place in Member States

18. Revised Guidelines on GDP - Consultation
Quality Management (Ch 1)
Senior management commitment
Management of outsourced activities
Risk management
Personnel (Ch 2)
Responsible Person
Organisation chart
Training in GDP
Operations (Ch 5)
Marketing Authorisation Holder (MAH) informed
Qualification of suppliers and customers

19. Revised 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 responsibilities
Transportation (Ch 9)
Delivery drivers trained in GDP
Maximum limit of 24 hours for transport hubs
Wholesalers distribution authorisation
Specific provisions for Brokers (Ch 10)
Register and have quality management system

20. GMP/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).

21. Regulations 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.

22. Barriers to traceability
Links between MAHs and Distributors
Brokers/Agents/Intermediaries
Documentation eg C of A
Commercial secrecy
Drug Master Files (DMFs)
Scope of Technical Agreements/Contracts
Complex and expensive technology options
Ownership of the process of change

23. Improvement 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 Distributors
Direction from sponsor companies (esp virtual)
Proper briefing and requirements specs for 3PLs.
Application of risk-based approaches to target resources at critical areas.

24. What is the long-term solution?
Integrate strategically upstream and downstream
Build shared processes and practices with business partners
Aim to look at principles behind the regulations and manage risk
Keep an end-to-end perspective on the supply chain at all times

25. Useful links
EU 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

26. Questions?
If there are any further questions, you can get to me in a number of ways:
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