supply chain qualification - sindusfarma · supply chain qualification rafik h bishara, ph.d....
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Supply Chain Qualification
Rafik H Bishara, Ph.D.
Technical Advisor
Chair, Pharmaceutical Cold Chain Interest Group
(PCCIG)
Parenteral Drug Association (PDA)
Sindusfarma / ANVISA / FIP-IPS
Brasilia, June 24-25, 2013
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Global Regulatory Requirements
Domestic Regulations
Global Regulations
Pharmacopeial Requirements
Industry Best Practices
Public Standards
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Regulatory and Standards-Based Guidance
Standards
USP <1079>, <1083>, <1118>
<1197>
IATA PCR, Ch. 17, 2009
AFF et SFSTP *. ISTA
Industry Best
Practices
PDA Technical Reports
39, 46, 52, 53, 58
Regulatory Guidance
Argentina
Australia
Austria
Bahrain
Brazil
Canada
China
Czech Rep.
Egypt
EU
FDA
ICH
India
Ireland
Italy
Jordan
Mexico
MHRA
Romania
Singapore
Saudi Arabia
S. Africa
S. Korea
UAE
Syria
Venezuela
WHO
Reference: Rafik H. Bishara, “The Impact of USP <1079> on Cold Chain Management”, March 7, 2006 (Sensitech Sponsored Webinar),
Revised January 17, 2013
* Guide Pratique: Chaine du froid du medicament
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ANVISA
National Sanitary Surveillance Agency
Resolution – RDC # 234, of August 17, 2005
2nd Article: “The importing company is liable for the quality,
efficacy, and safety of the imported lots of biological
products…”
3rd Article: “The importing company (registration owner) of
Finished Biological Products Lots… shall be exempted of
performing quality control tests…when meeting all the
following requirements.”
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ANVISA
National Sanitary Surveillance Agency (cont’d.)
3rd Article: (Paragraphs 1-7)
• 6th Paragraph: “The importing company (registration owner) must
present continuous recordings of the transport chain temperatures
proving that the product has been kept under recommended
storage and transport conditions.“
• “The temperature records shall identify the name of the product, the
number of the lot, time and date in which it was delivered and
received.”
• “The storage and transport conditions must be specified in the
Import License, according to the conditions established in the
registration of the finished biological product to be imported.”
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Increased Focus on End-to-End
Cold Chain Compliance
Republic of Argentina – Law 26,492 - Official Bulletin
• Enacted March 26, 2009 – Enforceable March 26, 2011
• “all medicine for human or animal use containing thermolabile
active principles must have a temperature indicator incorporated
in the individual container … that will provide confirmation that said
product has not lost the cold chain by the time it reaches the
consumer.”
• “The indicator will be installed by the factory and must remain on
the medicine, even on the individual consumer unit.”
• “For multidose packaging, the indicator must remain on the
container, so that the consumer can check to see that the cold
chain was not interrupted…”
Reference: Official Bulletin of the Republic of Argentina, Law 26,492 “Law for Regulating The Cold Chain of Medicine”,
March 26, 2009
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Increased Focus on End-to-End
Cold Chain Compliance (cont’d.)
Mexico Ministry of Health (MOH) – Official Letter
• “The cold chain report must correspond to the temperature of the
product , not to the external one.”
• “The devices that do not keep a punctual record of the temperature
during the whole transportation period will not be accepted as
neither those that activate the alarms for the temperatures above or
under the authorized temperature range in the labeling projects
(for example – Freeze Tag®, Reagent Stripes, etc.).”
• Mexican MOH only allowing use of data loggers not allowing use of
electronic or chemical indicators
Reference: Official Letter, Mexico D.F. , Commission of Sanitary Authorization, December 2007
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Saudi Arabia: Saudi Food and Drug Authority
Decree No. M/6 25/01/1428H, 01/07/1430H, 29/01/1427H
Ministry of Health and Customs General Department –
Placement of Temperature Measuring Gauge on Drug Shipments
“A temperature monitoring device must be placed for measuring
the shipment temperature and it shall be activated from the time
of shipment until the arrival of shipment to the point of entry”
Phase 1 – March 1, 2011 - Refrigerated (2-8 degrees Celsius)
Phase 2 – June 1, 2011 – “All drug shipments”
FAQ (Frequently Asked Questions for Temperature Monitors)
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Regulatory Oversight – World Health
Organization (WHO)
Technical Report No. 961, 2011
“Model guidance for the storage and transport of time- and
temperature–sensitive pharmaceutical products”
Table of Contents
Importation Warehousing Sites Storage Buildings Temperature-controlled storage Materials Handling Transport and Delivery
Labeling Stock Management General Procedures and Record Keeping Environmental Management Quality Management Personnel/Training
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IATA Label Revised October, 2009
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Regulatory Guidance Pushing Cold Chain
Visibility
Expanding In-Transit Monitoring Market
Manufacturing plant Raw materials Healthcare facility Wholesaler Distribution center Filling & packaging
Last Mile Distribution Raw Material / Manufacturing
Events
Traditional In-Transit Monitoring Market
Events
Revised USP General Chapter <1079>, Published 2012
“Good storage and distribution practices apply to all organizations and individuals
involved in any aspect of the storage and distribution of all drug products”.
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Product Attributes
Identity
Potency
Degradation Profile
Stability
• Accelerated
• Shelf Life
• Annual
• Cycling
• Freeze Thaw
Protein Denaturation
Sterility
Clarity & Color
pH Shift
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Packaging Development and Qualification
Types
• Primary Packaging
• Secondary Packaging
• Distribution Packaging
• Devices
Qualifications
• Component/Installation (CQ/IQ)
• Operational Qualification (OQ)
• Performance Qualification (PQ)
Requirements
• Temperature
• Time
• Payload
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Lane Qualification
• Lane Definition
• Study Protocol in Triplicates
• Verification
‒ Time in Transit
‒ Temperature
‒ Shock/Vibration
‒ Atmospheric Pressure
‒ Humidity
• Hot and Cold Profiles
• Modes of Transportation
‒ Air
‒ Truck
‒ Ocean Vessel
‒ Rail
• Testing
‒ Potency
‒ Degradation
‒ Sterility
‒ Clarity/Color
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Temperature Monitoring and Data Analysis
Monitoring
Data Collection
Analysis
Reporting
Excursions Evaluation
Corrective Action Preventive Action (CAPA)
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Good Distribution Practices (GDP)
Controlled Environment Logistics
• First Mile
• Last Mile
Examples of Supply chain Partners
• Manufacturers
• Distributors
• Importers/Exporters
• Hospitals
• Clinics
• Physician’s Office
• Pharmacies
• Patients
New EU GDP Guidelines
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Good Distribution Practices (GDP)
General
GDPs
Good Import
Practices
(GIPs)
Good Import
Practices
(GIPs)
Distribution
Control
Systems (DCS)
Distribution
Control
Systems (DCS)
Temperature
Control
Management
(TCM)
Temperature
Control
Management
(TCM)
GDP
Global Product
Protection
• Supply Chain Control and
Temperature Monitoring
• Cold Chain to
Temperature-Sensitive
• >30 GDPs
• Shipping Best Practices
• Inventory Management
• LSP/TSP Quality
Agreements
• CTPAT and Customs
• Certified Cargo Screening
Facilities
• Country of Origin Marking
• FDA Division of Import
Operations and Policy (DIOP)
member of Cargo Theft
Response Team (CTRT)
• GS1 Standards (GLN/GTIN)
• Track and Trace, Authentication,
Pedigree,
• Serialization,
• Cargo Security – In-Transit
Monitoring
• FDA SOP for Cargo Theft
• FDA Secure Supply Chain Pilot
Program (SSCPP)
• Pharmaceutical Cargo Security
Coalition (PCSC)
• TAPA (Transported Asset Protection
Association)
• Rx 360
Reference: David Ulrich, Distribution QA Director, Abbott – GDPs for an Ever Increasingly Complex Global Pharma Supply
Chain – GDP Overview MoH Regulations Discussion – Purdue University, April 14, 2012
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Supply Chain Integrity
Track & Trace
Pedigree
• Paper
• Electronic
Numerical Identifier
Authentication
Factors Affecting the Integrity
• Importation
• Anti-Counterfeiting
• Anti-Diversion and Theft
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Global Concern
There are world wide efforts to help protect the integrity of
medicine supply systems and ensure the safety of the
patient.
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Global Effort
Minimize risks that arise anywhere along the supply chain
which include:
• Sourcing of the pharmaceutical raw materials
• Manufacturing of the medicinal ingredients
• Finished dosage form
• Packaging
• Distribution to patient
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Good Supply Chain Integrity
•Encourage sound business practices
•Deter inference and manipulation by bad actors and illicit
people
•Provide effective means to detect adulterated drug
components and drug products
•Prevent adulterated materials from entering the complex
global pharmaceuticals and medical devices supply chain
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Supply System Integrity
•Challenge of drug diversion in the wholesale distribution
system
•Drug paper pedigree to identify prior sales, purchases, or
trades of drugs by anyone other than an authorized
distributor of record
•Electronic track-and-trace pedigree
•Standardized numerical identifier for prescription drugs
•Standards for identification, validation, authentication
tracking/tracing
•Quality systems
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Threats to the Supply Chain Integrity
•Insertion of counterfeit and adulterated medicines into
distribution channel
•Economic gain
•Purposes of terrorism
•Cargo theft of regulated products and their diversion for
illegal activities
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Factors Affecting the Supply Chain Integrity
I. Importation
II. Anti-Counterfeiting
III. Diversion and Theft
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Effective Supplier Partnerships
•Investigate supplier’s reputation
•Research supplier’s certification (e.g. ISO, Customs-Trade
Partnership Against Terrorism (C-TPAT), WHO)
•Determine supplier’s experience as a vendor in the
pharmaceutical industry
•Evaluate supplier’s Regulatory Compliance
•Invest in an early due diligence audit
•Establish Corrective Action Prevention Action (CAPA) Plan
•Quality Agreement
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Supply Chain Security Standards and
Measures
Risks of Logistics Security
Security Management
• Facilities
• In-transit
• Business Partners
• Data Management
• Human Resources
Standards
• Government (C-TPAT & AEO)
• ISO 28000:2007
• TAPA
• RX 360
Secured Shipments
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Global Cargo Theft Threats
Reference: FreightWatch International Supply Chain Intelligence Center, 2013 Global Cargo Theft Threat Assessment
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Brazil
One of the most violent
countries in regards to cargo
crime.
84% of incidents occur in Sao
Paulo and Rio de Janeiro
Cargo theft gangs are
becoming increasingly
specialized and are using
technology to carry out crimes
Most targeted products are
Food / Drinks, Electronics,
Tobacco and Pharmaceuticals
Reference: FreightWatch International Supply Chain Intelligence Center, 2013 Global Cargo Theft Threat Assessment
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Cargo Thefts in Brazil – Top Ten States
Some states do not report or
keep accurate crime statistics
State of Parana, for example, is
known in Brazil to have high
cargo crime incidents, but no
official statistics are published.
Reference: FreightWatch International Supply Chain Intelligence Center, 2013 Global Cargo Theft Threat Assessment
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Trends and Modi Operandi – Brazil
Hijacking continues to be primary method
• Notoriously violent
• Thieves sometimes carry better weapons than police and / or armed escorts
• Not uncommon to see armed confrontation
GPs jammers being used in an attempt to circumvent electronic
monitoring devices.
Criminals use internal information, mainly from transportation
companies’ employees, to obtain details of vehicles carrying high value
goods, the security measures in place, and the details of the escort
cars.
Warehouse thefts have been on the rise, although there are no official
statistics for this type of crime.
Reference: FreightWatch International Supply Chain Intelligence Center, 2013 Global Cargo Theft Threat Assessment
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Logistics Security Challenges
Smuggling of Contraband
Hijacking
Theft
Fire
Natural disaster
Accidents
Brand Integrity and Reputation
Government / Industry Compliance
Compliance audits for multiple programs
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Qualification Master Plan (QMP)
Test Profiles
Lane Qualification
Packaging Qualification
Operation Qualification
Performance Qualification
Evaluate Results
• Assay Tests
• Temperature Data
• Packaging Integrity
• Procedural Completion
Report
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Supply Chain Qualification
QMP
Supply Chain Security
Supply Chain Integrity
Good Distribution Practices
Temperature Monitoring and Data Analysis
Lane Qualification
Packaging Development and Qualification
Product Attributes
Global Regulations
