Good Distribution

Practices: What do
they mean to you?

Presented by: Hedley Rees, Biotech PharmaFlow,

UK
 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
DISTRIBUTION IN
PHARMACEUTICALS

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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
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
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
 Distribution in a Nutshell

Storage & Transportation

E2E Supply Chain

WHY HAS GDP BECOME SUCH
A HOT TOPIC?

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 The Supply Chain Fragments….
• 1970's:
– 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.
Dis-integration of the supply chain

•Outsourcing begins in earnest…..

Patients
 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.
 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 28 2011
 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.
 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).
WHAT IS THE CURRENT GLOBAL
LANDSCAPE?
 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
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

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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
 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
 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).
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.
 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

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 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.

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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
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EU GDP Consultation:
Useful links
http://ec.europa.eu/health/files/eudralex/vol-4/2011-07_gdpguidline_publicconsultation.pdf
Responses to EU GDP Consultation:
http://ec.europa.eu/health/human-use/good_distribution_practice/developments/2011_pc_gdp_en.htm
EU Good Manufacturing Practice Directive (2003/94/EC):
http://ec.europa.eu/health/files/eudralex/vol-1/dir_2003_94/dir_2003_94_en.pdf
EU Good Distribution Practice Directive (94/C 63/03):
http://ec.europa.eu/health/files/eudralex/vol-4/gdpguidelines1.pdf
EU GMP/GDP:
http://www.ema.europa.eu/ema/index.jsp?
curl=pages/regulation/document_listing/document_listing_000154.jsp&mid=WC0b01ac0580027088
&jsenabled=true
DIRECTIVE 2001/83/EC OF THE EUROPEAN PARLIAMENT
http://www.emea.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2009/
10/WC500004481.pdf
Supply Chain Management in the Drug Industry: Delivering Patient Value for Pharmaceuticals and
Biologics, J Wiley & Sons, NJ, February 2011.
http://www.amazon.com/Supply-Chain-Management-Drug-
Industry/dp/0470555173/ref=pd_rhf_gw_p_t_1

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 Questions?
If there are any further questions, you can
get to me in a number of ways:
T: +44(0)1656 667710
M: +44(0)7718 884816
E: h.rees@pharmaflowltd.co.uk
W: http://www.pharmaflowltd.co.uk
LinkedIn:
http://www.linkedin.com/profile/view?
id=2432076&trk=tab_pro