Download Good Distribution Practices in the EU and U.S. — How do they Differ?

Good Distribution Practices
in the EU and U.S. —
How do they Differ?
Cormac Dalton, Director of
Compliance, Supply Chain and
Commercial QA, AbbVie Ireland
(AbbVie Ltd)
Global GDPs - A risk based
approach to management of
distribution
Cormac Dalton, Abbvie
International Pharmaceutical Distribution
Conference
Sept 13th 2016
Agenda
1. What do the regulations say
2. Where GDPs & GMPs meet
3. ICH Q9 – Quality Risk Management
4. Temperature management
What are the GDPs?  GDP Dashboard
GDP's
Regulations
Countries
Argentina
Brazil
Mexico
Australia
General
GDPs
GIP
TCM
Importation
DCS
Storage Buildings / Warehousing
Quality Systems
Transport, Delivery, Storage
Labeling
Inventory Procedures
Exception Product Return,
Recall,
Port
General
Loading &
Temperature Product Temperature- Humidity Shipping General
Qualified
Good
Stock Management &
GPS and
Traceability /
Building General
Packaging,
Serialization
GS1
Product
Withdraw,
Handling / Offloading
Layout /
Receiving
Monitored
Stability Controlled Control and Containers Lableling
Personnel, Documentatio Control
Bulk Security,
Stock
Cleanliness Security
Prcoessing
& ePedigree
Identification
Control and
Customs
Contruction
Bays
Storage Areas Profiles
Transport Monitoring & Packing Relabeling
Training n Practices Systems Compaint
Counterfeits
Tracking
Procedures
Disposal
There are core elements to all world-wide GDPs
 just like there are core elements to other GxPs (e.g. cGMPs):
1. Quality Management
2. Process
3. Validation / Qualification (process, cleaning, E/U/F)
4. Verification e.g. Audits (Internal and External)
LAA Region
Regulating the Cold Chain of Medicines (Ley
Resolution - RDC No. 234
Guidelines for Imported Biotechnological &
Code of Good Wholesaling Practice for
Cold Chain Pharmaeutical Products
India (OPPI) Guideline on Good Distribution Practices for
Japan
Biological Pharma Revision H15.5.15
Malaysia
Guidelines on Good Distribution Practice
Singapore Guidance Notes on Good Distribution
South Africa Good Whilesaling Practice for Wholesales,
Phillipines
Adoption and Implementation of the World
Central European Region
Austria
Austrian GDP Regulations
Czech
Guidelines for Correct Distribution of Human
Republic
Czech GDP Guidelines
EMA
European Medicines Agency: " QP
Guidelines on Good Distribution Practice of
Directive 2001/83/EC of the European
EU
The IPEC Good Distribution Practices Guide
Europe - Good Distribution Practices Audit
Rx-360 Summary of IPEC GDP
Ireland
Guide to Control and Monitoring of Storage
Switzerland Distribution of Temperature Controlled
North American Region
Canada
Guidelines for Temperature Control of Drug
FDA to Revise Component GMPs to Bolster
United States Bar Code Technologies for Drugs and
Standards for Securing Drug Supply Chain...
Middle-Eastern European Region
Egypt
Minster Decree for Wholesalers - Circular
Pharmacist Regulations - Circular 6
Israel
Status of Current GDP Regulations in Israel
Romania
NMA No. 30/24.09.2009
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Saudi Arabia, GCC Guidelines for Stability, PP-SPC-9031,
Saudi Food & TOPA GTS - 6000
Drug Authority
UAE
Circular No. 246-2011
International Health Organizations
Updated Policy on Returns of Non-Defective
Guidance on Preventing Breaches in the
MHRA
Cold Chain Distribution GDP Risk
GDP Risk Assessment Strategy
Regulatory Provisions for Quality Controlled
Model requirements for the storage and
WHO
New Guidance for storage and transport of
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Good Distribution Practices (GDPs)
Good Import Practices (GIPs)
Product Protection
Temperature Control Management (TCM) Distribution Control Systems (DCS)
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What is it? Where did it come from? Is it allowed to come into commerce?
Can you prove it is what you say it is?
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They are a “Logical” extension of the GMPs
GDP's
Regulations
Countries
Argentina
Brazil
Mexico
Australia
General
GDPs
GIP
Importation
TCM
DCS
LAA Region
Regulating the Cold Chain of Medicines (Ley
Resolution - RDC No. 234
Guidelines for Imported Biotechnological &
Storage Buildings / Warehousing
Quality Systems
Transport, Delivery, Storage
Labeling
Inventory Procedures
Exception Product Return,
Recall,
Port
General
Loading &
Temperature Product Temperature- Humidity Shipping General
Qualified
Good
Stock Management &
GPS and
Traceability /
Building General
Packaging,
Serialization
GS1
Product
Withdraw,
Handling / Offloading
Layout /
Receiving
Monitored
Stability Controlled Control and Containers Lableling
Personnel, Documentatio Control
Bulk Security,
Stock
Cleanliness Security
Prcoessing
& ePedigree
Identification
Compaint
Control and
Customs
Contruction
Bays
Storage Areas Profiles
Transport Monitoring & Packing Relabeling
Training n Practices Systems
Counterfeits
Tracking
Procedures
Disposal
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• Good Distribution Practices (GDPs)
• Good Import Practices (GIPs)
• Security Audits & Supply Chain
• Export Controls
GPP
Controls
• Marketing Authorization and License
Global
Control
Code of Good Wholesaling Practice for
Cold Chain Pharmaeutical Products
India (OPPI) Guideline on Good Distribution Practices for
Japan
Biological Pharma Revision H15.5.15
Malaysia
Guidelines on Good Distribution Practice
Singapore Guidance Notes on Good Distribution
South Africa Good Whilesaling Practice for Wholesales,
Phillipines
Adoption and Implementation of the World
Central European Region
Austria
Austrian GDP Regulations
Czech
Guidelines for Correct Distribution of Human
Republic
Czech GDP Guidelines
EMA
European Medicines Agency: " QP
Guidelines on Good Distribution Practice of
Directive 2001/83/EC of the European
EU
The IPEC Good Distribution Practices Guide
Europe - Good Distribution Practices Audit
Rx-360 Summary of IPEC GDP
Ireland
Guide to Control and Monitoring of Storage
Switzerland Distribution of Temperature Controlled
North American Region
Canada
Guidelines for Temperature Control of Drug
FDA to Revise Component GMPs to Bolster
United States Bar Code Technologies for Drugs and
Standards for Securing Drug Supply Chain...
Middle-Eastern European Region
Egypt
Minster Decree for Wholesalers - Circular
Pharmacist Regulations - Circular 6
Israel
Status of Current GDP Regulations in Israel
Romania
NMA No. 30/24.09.2009
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• Cold Chain  End-2-End Supply Chain
Management
Saudi Arabia, GCC Guidelines for Stability, PP-SPC-9031,
Saudi Food & TOPA GTS - 6000
Drug Authority
UAE
Circular No. 246-2011
International Health Organizations
Updated Policy on Returns of Non-Defective
Guidance on Preventing Breaches in the
MHRA
Cold Chain Distribution GDP Risk
GDP Risk Assessment Strategy
Regulatory Provisions for Quality Controlled
Model requirements for the storage and
WHO
New Guidance for storage and transport of
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• GS1, Track and Trace, Serial
Number Mgmt., Trade Relations
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Product
Temperature Control Management
• Distribution Control Systems
Protection
(TCM)
(DCS)
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Core areas of focus for GDP
1. General GDPs
2. Temperature Control
3. Trade Controls (import/export)
4. Supply Chain Traceability
5. Supply Chain Risk Management
Falsified Medicines Directive (2011/62/EU)
• Definition of a falsified medicine:
Any medicinal product with a false representation of:
(a) its identity, including its packaging and labelling, its name or its
composition as regards any of the ingredients including excipients and
the strength of those ingredients;
(b) its source, including its manufacturer, its country of manufacturing,
its country of origin or its marketing authorisation holder; or
(c) its history, including the records and documents relating to the
distribution channels used.
Structure of EU GDP Guideline
Chapters
Introduction:
1.
Quality Management
2.
Personnel
3.
Premises and Equipment
4.
Documentation
5.
Operations
6.
Complaints, Returns, Falsified Medicinal Products and Recalls
7.
Outsourced Activities
8.
Self-Inspections
9.
Transportation
10. Specific Provisions for Brokers
Supply Chain Maps – where do you ship your product from - to
2012 – European Commission: Health and Consumers Directorates Central
EU GDPs (Good Distribution Practices)
•
Commission Guidelines on Good Distribution Practice of Medicinal Products for Human Use
 Approval – Dec. 2012, effective June 2013
 Sec. 5.4 “… The supply chain of medicinal products should be known and
documented.”
 Stresses GMP, supply chain security and temp mgt
Supply Chain Maps
Control of APIs (Active
Good Distribution
Pharmaceutical
Practices
Ingredients)
Issued March 2013
Importation
FalsifiedRe-issued Nov. 2013
Medicine
Directive
Safety Features
Barcodes and TEP
(Tamper Evident
Packaging)
Internet Sales
Supply Chain Mapping – Annex 16 EU GMP
• The entire supply chain of the active substance and medicinal
product up to the stage of certification is documented and available
for the QP.
• This should include the manufacturing sites of the starting materials
and packaging materials for the medicinal product and any other
materials deemed critical through a risk assessment of the
manufacturing process.
• The document should preferably be in the format of a
comprehensive diagram, where each party, including subcontractors
of critical steps such as the sterilisation of components and
equipment for aseptic processing, are included.
Supply Chain Mapping – Distribution
• Same philosophy for distribution:
• Routes
• Carriers / contractors
• Conditions
• End-to-end approach = knowledge!
EU GMP – Annex 15: Qualification and Validation
Verification of Transportation in the EU GMP
6. VERIFICATION OF TRANSPORTATION
6.1. Finished medicinal products, investigational medicinal products, bulk
product and samples should be transported from manufacturing sites in
accordance with the conditions defined in the marketing authorisation, the
approved label, product specification file or as justified by the manufacturer.
6.2. It is recognised that verification of transportation may be challenging due
to the variable factors involved however, transportation routes should be
clearly defined. Seasonal and other variations should also be considered
during verification of transport
Verification of Transportation in the EU GMP
6. VERIFICATION OF TRANSPORTATION
6.3. A risk assessment should be performed to consider the impact of variables
in the transportation process other than those conditions which are
continuously controlled or monitored, e.g. delays during transportation, failure
of monitoring devices, topping up liquid nitrogen, product susceptibility and
any other relevant factors.
6.4. Due to the variable condition expected during transportation, continuous
monitoring and recording of any critical environmental conditions to which the
product may be subjected should be performed, unless otherwise justified.
Scenario
• A short-term temperature excursion during the transport of a
product from a third country to the EU.
• The label claim for the product is ‘store below 25°C’, and the
excursion was up to 29°C for 3 days.
• Existing stability data demonstrated no issues when stored at 30°C
for up to 3 months.
• Is this an ‘unexpected’ or ‘expected’ deviation (in terms of
definitions within Annex 16)?
Scenario (continued)
• This situation would fall within the scope of ‘unexpected deviations’,
provided that the shipment process was designed to comply with
the registered conditions (i.e. that the excursion could be reasonably
described as ‘unexpected’).
• However if there were no controls over shipment conditions, then
the use of stability data as a ‘routine’ means to justify such an
excursion would not be acceptable.
• Understand the risks and address with the appropriate risk control
strategy.
•
https://mhrainspectorate.blog.gov.uk/2015/12/07/transportation-of-medicinalproducts-some-things-to-consider/
ICH Q9 – Quality Risk Management
Storage, logistics and distribution conditions
• To assess the adequacy of arrangements to ensure maintenance of
appropriate storage and transport conditions (e.g., temperature,
humidity, container design);
• To determine the effect on product quality of discrepancies in
storage or transport conditions (e.g., cold chain management) in
conjunction with other ICH guidelines;
• To maintain infrastructure (e.g., capacity to ensure proper shipping
conditions, interim storage, handling of hazardous materials and
controlled substances, customs clearance);
• To provide information for ensuring the availability of
pharmaceuticals (e.g., ranking risks to the supply chain).
Definition: Risk Management
Identify, characterize, and
assess threats
Assess the vulnerability of
critical assets to specific threats
Determine the risk (i.e. the
expected consequences of
specific types of attacks on
specific assets)
Identify ways to reduce those
risks
Prioritize risk reduction
measures based on a strategy
Know what use you are developing the data for!
Know failure points
How the product reacts at highs (50C) and lows (-20C)
That will help determine level of control needed during shipping
Control the storage label
E.g. CRT Stability Budget (Knowledge)
So when the inevitable happens…..
Options for CRT shipping
1. Active shippers
2. Passive shippers
3. Blankets
4. Controlled networks
5. Risk it
Bulk Drug Shipment Temp Monitoring (Stability Budget)
Mean ambient temperature at
O’Hare on 6/22/2014: 21.17°C
Held by Port (CBP, MoH, etc))
Pack out at Mfg’ing site
Transport to packaging site
Mean ambient temperature at
Airport on 6/19/2014: 16.11°C
Belly of plane
Arrival at packaging site
Passive Shippers – one origin, multiple destinations
Internal & External Monitoring – Know your product and know your data
Tarmac
handling
Loading
final
unloading
Example of multiple shipments – same origin and destination
Need to know your supply chain temps and
How your product reacts
Summary / Conclusion
• Global expectation surrounding GDPs are increasing
• Have & maintain the knowledge
• Supply chain
• Risks (intrinsic & extrinsic)
• Label claims
• Stability data
• Embrace risk management & mitigation
• Patients need medicinal products!