Global Good Distribution Practice Update

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
CFR-21
WHO GDP guide is often used by default when
country or regional guidance is not published
Guide 0069
Guide Pratique Chaine du froid du medicament
Reference Rafik H. Bishara, The Impact of USP
lt1079gt on Cold Chain Management, March 7, 2006
(Sensitech Sponsored Webinar), Revised
March 21, 2010
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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

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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 211.80, 150
  820.65, 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, FDC 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

8
Cold Chain Protection

• Key Topics
• 21CFR 211.142
• 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

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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

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Supply Chain GDP Guidance

• Implement effective cold-chain management to
  ensure a products 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 www.pda.org
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

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

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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

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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)