Global Good Distribution Practice Update

Karl KussowManager, Quality: FedEx Custom Critical

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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.

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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

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Regulatory and Standards-Based Guidance Driving GDP…

StandardsUSP <1079>

IATA PCR,ISTA,AFF et SFSTP *

Best PracticesPDA TR No. 39,

46, 52,53

Regulatory GuidanceArgentinaAustraliaAustriaBrazilCanadaChinaCzech Rep.

EgyptEUFDAICHIndiaIrelandIsraelItalyMexico

MHRARomaniaSingaporeSaudi ArabiaS. AfricaS. KoreaVenezuelaWHO

* Guide Pratique: Chaine du froid du medicament

Reference: Rafik H. Bishara, “The Impact of USP <1079> on Cold Chain Management”, March 7, 2006 (Sensitech Sponsored Webinar), Revised March 21, 2010

CFR-21

Guide 0069

WHO GDP guide is often used by default when country or regional guidance is not published

European Directive for GDP transport and storage -- dir_2003_94_en

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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

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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, 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

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Cold Chain Protection

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

Key Topics:21CFR 211.142•Store in appropriate conditionsWHO 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

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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 product’s safety, efficacy, and pedigree are not affected by the distribution process.

PDA TR-52Topics addressed by the guidance3.0 Requirements3.1 Stability3.1.1 Storage Temperatures3.1.2 Shipping Temperatures3.1.3 Stability Testing to Support Distribution3.2 Distribution Control Management3.3 Performance Management3.4 Supply Chain Partner ManagementTable: Seven Pillars of Good Distribution Practices

Source: PDA Technical Report No. 52 , Guidance for Good Distribution Practices (GDPs) For the Pharmaceutical Supply ChainPurchase online from the PDA at www.pda.org

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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.

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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

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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)