1. Global Good Distribution Practice Update
Karl Kussow
Manager, Quality:
FedEx Custom Critical

2. GDP Highlights “Cold Chain” to “Temperature-Control Chain” Monitoring
Security / Serialization
Quality Agreements
Complexity due to many countries and organizations, despite their common objective
Disclaimer: This presentation is not legal advice. Please seek appropriate legal counsel for answers to your regulatory compliance questions.

3. Elements of Good Distribution Practice (GDP)
Security
Pedigree
Environmental monitoring
Temperature control
Auditable data record
Data access (QA/QP release, International Customs)
Quality systems
Procedures and Training for sustainability and continuous improvement
Flexibility for individual products

4. Regulatory and Standards-Based Guidance Driving GDP…
European Directive for GDP transport and storage -- dir_2003_94_en
Standards
USP <1079>
IATA PCR,ISTA,
AFF et SFSTP *
Best Practices
PDA TR No. 39,
46, 52,53
Regulatory Guidance
Argentina
Australia
Austria
Brazil
Canada
China
Czech Rep.
Egypt EU
FDA
ICH
India
Ireland
Israel
Italy
Mexico
MHRA
Romania
Singapore
Saudi Arabia
S. Africa
S. Korea
Venezuela
WHO
CFR-21
WHO GDP guide is often used by default when country or regional guidance is not published
Guide 0069
Also:
India OPPI (Organization of Pharmaceutical Producers of India) Guidelines (for) Cold Chain Pharmaceutical Products
New -- South Africa has produced a draft that they have sent for comment.  I do not plan to comment on this one, but have attached it here in case you would like to review it. It is targeted to be effective in July 2012.
In the spirit of every country calling their guidance by a different name, they call theirs; “GOOD WHOLESALING PRACTICE FOR WHOLESALERS, DISTRIBUTORS and BONDED WAREHOUSES”
This is similar to the new EU GDPs, but more thorough and stress that the GDP is the responsibility of the wholesalers (i.e. wholesaler needs to confirm compliance from the pharma supplier)
* Guide Pratique: Chaine du froid du medicament
Reference: Rafik H. Bishara, “The Impact of USP <1079> on Cold Chain Management”, March 7, (Sensitech Sponsored Webinar), Revised March 21, 2010

5. Security: A Growing Concern
Cargo Screening (TSA and Local Countries)
100% screening
Access controls
Chain of custody
Customs Trade Partnership Against Terrorism (C-TPAT)
Supply Chain Security Guidelines
Anti Counterfeiting / Diversion (HHS/FDA, CBP)
Standardized Numerical Identification / Serialization
E-Pedigree
PREDICT, Good Importer Practices
HHS/FDA: US Dept. of Health and Human Services, Food and Drug Administration
CDER: Center for Disease Evaluation and Research
CBER: Center for Biologics Evaluation and Research

6. Security and Temperature: VISIBILITY + CONTROL
Controls have similar characteristics
Chain of Custody
Monitoring systems: real time for situational awareness
Track and Trace
Alert mechanisms: overlapping tiers
Clear instructions with training
Procedural controls
Ability to react to protect cargo while enroute

7. Traceability
Know where the products are and verify they are the same as shipped
Some requirements found in 21 CFR , 150; , 86
Containers indentified with a distinctive code and current status
Defined distribution system
Identify units in order to facilitate corrective action
Verify status at every step from mfg to end user
Only continue to distribute accepted units
Anti-Counterfeiting and Diversion prevention a priority of FDA
April 28, 2010, Letter: FDA Urges Industry to Prevent Cargo Theft
March 2010, FDA Guidance: Standardized Numerical Identification for Prescription Drug Packages
September 27, 2007, FD&C Act amended: FDA required to develop standards …for the purpose of securing the drug supply chain against counterfeit, diverted, subpotent, substandard, adulterated, misbranded, or expired drugs
Complex global supply chains, international trade, the foreign sourcing and manufacture of regulated products, and the increase in the volume and complexity of imported products
have forced FDA to reevaluate its approach to supply-chain safety. We have seen the warning signs: contaminated heparin, melamine-tainted milk products, counterfeit glucose monitor test strips, to name just a few. 
Globalization presents a host of internal and external challenges to the design, development, manufacturing, and distribution of regulated food and medical products—challenges that impede the prevention, detection, intervention, and response to product safety

8. Cold Chain Protection Key Topics:
21CFR
Store in appropriate conditions
WHO QAS/04.068
GDP applicable to all pharmaceutical products
Temperature mapping of vehicles
Health Canada Guide 0069
Supply-chain rules
Temperature monitoring of distribution chain
Brazil
For import release, all incoming biological products must have temperature-monitoring records showing proper storage temperatures. EU
Ensure storage conditions at all times
Controlled temperature products (15-25 °C) should be transported by appropriate means
Temperature review is part of QP release
Integrated Approach to temperature protection
Stabilize the ambient temperature profile through procedure
Contingency Response through near-real-time monitoring
In-transit infrastructure / procedure
Temperature records
Easily available upon arrival at port of entry for customs/regulatory release
Balance Product stability, Process Control, and Package

9. Country Regulations and Guidance: Continued Development
Ireland
Medicinal products should be stored and transported under conditions which ensure that their quality is maintained
EU (GDP guide)
Ensure storage conditions at all times. Controlled temperature products (15-25 °C) should be transported by appropriate means
Saudi Arabia and Brazil very similar
Electronic datalogger in every shipment
For import release, all incoming biological products must have temperature monitoring records showing proper storage temperatures
India
Constant temperature monitoring
Refrigerated vans should be qualified. Qualification should be done by keeping sufficient temperature monitors to cover all parts of the van
Product Serialization
United States, Europe, Turkey, Brazil and India

10. GDP Quality Systems – Recent Updates
Canada, Guide 0069, Updated January 2011
Label claim and Transport environmental requirements supported by stability and technical justification. [1.0, 2.0]
ANY environmental category
Qualified equipment / environmental controls [3.1, 3.2**, 3.3*]
Calibration, Monitor locations, alarms, recorded [3.1, 3.2, 3.3]
Properly loaded [3.1]
Protect from weather during transfer (load/unload) [3.2, 3.4]
Written agreements / procedures [2.0, 3.1, 3.2, 3.5]
Training [3.1]
Transportation Records including monitoring records [3.5]
Audits [3.2]

11. Supply Chain GDP Guidance
Implement effective cold-chain management to ensure a product’s safety, efficacy, and pedigree are not affected by the distribution process.
PDA TR-52
Topics addressed by the guidance
3.0 Requirements
3.1 Stability
3.1.1 Storage Temperatures
3.1.2 Shipping Temperatures
3.1.3 Stability Testing to Support Distribution
3.2 Distribution Control Management
3.3 Performance Management
3.4 Supply Chain Partner Management
Table: Seven Pillars of Good Distribution Practices
Source: PDA Technical Report No. 52 , Guidance for Good Distribution Practices (GDPs) For the Pharmaceutical Supply Chain
Purchase online from the PDA at

12. IATA Perishable Cargo Regulations Chapter 17
Safeguarding the temperature-control chain
Service Level Agreement
Common Quality Systems expectations
Label provides consistent identification of temperature-sensitive pharma cargo with the correct handling instructions to care for them
Shipment-specific temperature instruction noted here.

13. Quality Agreements – tool for communication and compliance
Common to regulation, standard, and best practice guidance
Integrate competing viewpoints:
Product vs. Service Level
Quality Agreement
specific to transport
Service Guide as resource

14. Temperature-Control Transportation Best Practice
Quality Management System
Communication
Real time
Transparent access
Manual and automated alarms
Qualified equipment
Mapped vehicles
Properly located temperature monitors
Calibrated monitors
Properly trained personnel
Balanced Process: Risk, Product / Compliance, System / Equipment Capability
Compliant audit record

15. Challenges for HPCL industry
Temperature Control = not just “Cold” Chain
Quality System activities:
Pre-shipment (SOP/Agreement and Qualification)
Enroute (Exception Detection, Intervention)
Post shipment (Investigation and CAPA)
Integrated Approach
Service level integrated with product requirements
Options to achieve the right balance
Value: quality, risk, protection, controls, flexibility, sustainability, scalability, cost
Temperature Controls: Packaging/Container
Temperature Controls: Transport Service Level
Controls
Transit time
Temperature profile
Contingency response options

16. Opportunities for Transportation
Temperature-control infrastructure
Enhanced controls during transport
Improved contingency response
Combine data streams into one interface for monitoring and reporting
Temperature (and other environmental factors as needed)
Location
Status (who has custody right now)
Door-open (and/or light)
Identity confirmation (enabling authentication at delivery)