Managing Multi-Use Thermo Container Systems as Part of the ...

Managing Multi-Use Thermo Container Systems
as Part of the Pharmaceutical Quality System
Best Transport Practice for Pharma Packaging
Compliance Webinar
February 21st, 2013
Volker Kirchner
World Courier (Deutschland) GmbH
Operations Director NCEE

Agenda
• Active vs. passive packaging systems (pros and cons)
• Multi-use systems (procedures / problems / solutions)
• Cleaning / disinfection procedures
• Maintenance
• Performance control / requalification

GxP Requirements for Pharmaceutical Products
Manufacturer
GMP / GSP
Logistics Partners
GDP / GSP
Customer / Hospitals
GCP / GSP

Risk Management
• Force Majeure Risks: external risks can not be influenced
Natural disasters, strikes, terrorism, wars
•Climatic impact: Environment
Weather, climate, season
• Supply- and Process Risks:
Depending on the selected thermo container system
Transportation modus (aircraft, ship, truck, train)
Transit time
Human- language skills. Information exchange: Qualified and trained personal
Counterfeits, theft
• Demand Risks: Market / customer related

Innovative Supply Chain

Temperature Ranges
-196°C - liquid nitrogen shippers / dry shippers (-180°C)
-80°C - Dry ice
-40°C - PCMs
-20°C - Gel packs / PCMs
+2° to +8°C - Gel packs / PCMs
+15° to +25°C - PCMs
+37°C - PCMs

Potential solutions
Packaging
• Active Systems
• Semi-active Systems
• Passive Systems
• Single / Multiple Use
7

Active Systems
• Respond actively to changes in temperature
• Require electricity to measure and influence
temperature
• Can have moving parts (fan)
• Can utilize dry ice (DG) for cooling
• Usually large, multi-use units
• Not highly insulated due to their nature
• Examples: Envirotainer, reefer trucks

Example: Envirotainer / Unicooler
• Active Systems - Unit Load Devices (ULD)
• +2°C to +8°C
• +5°C to +30°C
• -20°C to +30°C
• Uses dry ice to cool, operated by fans
• Unicooler can additionaly heat
• Reusable Systems

Active Systems - Summary
Pros
• For pallet commodity
• No preconditioning of gel packs is necessary
• Newer models have active heating as well as cooling systems
Cons
• Limited insulation – susceptible to external temperatures
• Customs and operator restrictions
• Multi-Use system need to be cleaned and maintained after each transport
• Susceptible to loss of power, loss of coolant, mechanical breakdown
• Not all systems are redundant

Semi-active Systems
• Generally single-use packaging
• +2° to +8°C shipments
• Use both refrigerated as well as frozen gel packs
• Polystyrene or polyurethane boxes
• Often used for “final-leg” transports
• Can’t regulate energy release
• Susceptible to colder environments

Semi-active Systems - Summary
Pros
• Low cost
• Low weight
• Single use, need no cleaning and maintenance
Cons
• +2° to +8°C different configurations – winter / summer times
• Low thermal and physical stability

Passive Systems
• Single- or multi-use packaging
• Various temperature ranges
• Generally use Phase Change Material gel packs
• PCMs conditioned to product temperature
• Can be easily stored in cooler / freezer
• High degree of security and protection
• Higher weight, physically robust

Example 1: Credo Cube
• Passive system
• Phase Change Material PCM
• +15°C to +25°C
• +2ºC to +8ºC
• -15°C to -25ºC
• Hard case, reusable outer shell
• Removable outer box
• Vacuum Insulated Panels
• Different sizes

Credo Cube - Summary
Pros
• Good cost/benefit performance
• Lower weight
• No state and operator restrictions
• No different configurations for summer or winter
Cons
• Sensitive against external influences
• Locking only possible for largest system
• Check each system for physical stability
• Block loading is not possible
• Maintenance and cleaning

Example 2: VIP TCS

Pros VIP TCS Multi-use
• no state- and operator restrictions
• ball corners to prevent direct contact to earth surface
• One configuration for summer- and winter times
• Physical stability
• Block loading
• Tainer- and cases are stackable for fork lifts on a
permanent pallet

Cons VIP TCS Multi-use
• Higher weight
• VIP Multi-use are rentable systems and need to return after delivery
• Multi-use units need maintaining and cleaning
• Vacuum Insulation Panels between inner – and outer container are
not visible

VIP PCM Types
Phase Change Material (PCM )
► High performances Phase Change Material with longer temp slot
availability
► Conditioned to same temperature as the product
► Conditioning by courier’s or customer’s trained staff, according to
SOP

PCM and Temp Probe Conditioning

Multi-use TCS Packaging and Labelling
• Labelling
• Place PCMs into unit according to SOP
• Initial start of the conditioned temperature monitor
• Place the conditioned product into the TCS

PCM Types in Multi-use Systems
Qualified transit times for transport of temp-controlled samples between (+2º to +8ºC):
VIP TCS
Outside
Temperature
Number of PCMs
Qualified time
VIP-box 3L
+35°C (± 1°C)
+20°C (± 5°C)
-5° C (± 1°C)
6 x 10L+04G
82 h
120 h
59 h
VIP-box XL
(45L)
+35°C (± 1°C)
+20°C (± 5°C)
-5° C (± 1°C)
24 x 10L+04G
93 h
120 h
64 h

Qualified Transit Times Credo TCS
Transport of temp-controlled samples between + 2º to +8ºC
• Payload capacity 56 L / 25 kg
• Payload area DIMS (LxWxH)
38,1 x 38,1 x 38,1 cm
• Payload exterior DIMS (LxWxH)
53,3 x 49,5 x 50,2 cm
• Modular TIC® walls with integrated
phase change material
• Series 4 – 5696 (Credo Cube)
• Thermal performance 96 hours
in summer profile (+22° to + 35°C)

Evaluation Temperature Monitoring

Multi-use TCS Cleaning

Multi-use Cleaning and Disinfection
• Multi-use TCS need to be cleaned after each transport
• Cleaning of the systems according to SOP
• Disinfection of the inner – and outer containers
• Using of coloured labels in order to differentiate disinfected from not
disinfected units
• Documentation of cleaning
• Administration of the units by serial number

Multi-use Performance Control
• Performance test of systems by temperature monitoring with each transport
• PCM discharge control
• Green label – ready to use

Multi-use TCS Requalification
• Identification by serial number
• Servicing in a maintenance department, if damages are visible
• Continuous visible inspection for possible contamination and replacement
of PCMs when necessary
• Regular control of transport frequency and unit age by serial number and
list examination by logistics partner or customer

Examples Using Multi-use TCS
• Investigational Drugs
• Medical products
• Biological products and substances
• Vaccines
• Replacements
• Clinical supplies with restrictions about the stability of the product

Multi-use Systems Protect the Environment

Quality Systems
• Quality Management
• Environment Management
• Storage Management
• Transportation Management
• Risk Management
31

Quality Management
QMS Trained staff Equipment
GDP & ISO Training / testing Qualified/calibrated
32

People
• Education
• Training
• Experience
• Test for Effectiveness
• Recurring Training
• Documentation

P # y-m-d SOP/Topics FAQ #
01 09-08-01 SOP Creation, Review + Distribution
02 10-01-01 Acceptance and Service Restrictions
03 10-01-01 Dangerous Goods - Shipping Restrictions
SOP Topics
04 09-09-15 Fridges and Freezers for Pre-Conditioning of Gel Packs
05 09-09-15 Preparation of Gel Packs for Use
06 09-09-15
Selection and Use of Gel Packs within Temperature Controlled Shipment
Packaging
07 09-09-15 Dry Ice Information and Handling
08 09-08-01 Special Handcarry
09 09-08-01 Shipment Value/Currency + Weight/Dimensions
10 10-05-15 Handling of T2 Envirotainers
11 10-05-15 Handling of e1 Envirotainer
12 09-09-15 Dry Shipper Handling
13 09-11-16 GDP Compliant Documentation
14 09-11-16 Premises and Equipment
15 09-11-16 CAPA (Corrective And Preventive Action)
16 09-11-16 Change Control Management
17 09-11-16 External Audits
18 09-11-30 Self Inspection
19 09-11-16 Management of Outsourced Activities and Purchased Materials
20 09-11-30 Training Program
21 10-05-01
KPI and Incident Reporting Monitoring Process Performance and Product
Quality
22 09-11-30 Management Review Meeting
23 10-05-01 VIP TCS Cleaning Procedure
25 10-08-01 Internal Audits
30 09-09-01 Selecting and Preparing Temperature Monitors
31 09-09-01
32 10-05-17
Starting Temperature Monitors, Positioning Monitors inside Shipments and
Recording this Information
Recovering Temperature Monitors, Recovering and Distributing Data,
Storage of Used Monitors
032
27 Computer Backups and Disaster Recovery - see INET MIS

Challenges of Multi-use Systems
Challenges of using multi-use systems can
only be overcome in a strong network with well
developed quality management systems and
highly motivated and trained people!
35

Vielen Dank!

GxP in Transportation
Good Distribution Practice and Regulatory Compliance
In International Biopharm Logistics
37
Global Webinar
21 February 2013

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
World Courier
GxP Presentation
Presentation Outline
1. Why GxP?
A short history of how GMP evolved
2. The poor relations
GSP and GDP enter the scene
3. The shifting Focus
Regulatory Updates
4. Daily Distribution Challenges
How to ask the right Questions
5. Potential Solutions
A Look at GxP compliant services
38

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP?
A short history of how
GMP evolved
39

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP | A short history of how GMP evolved
Definitions – GxP
GxP is a general term for Good Practice quality guidelines and
regulations.
These guidelines are used in many fields, including the
pharmaceutical and food industries.The titles of these good
practice guidelines usually begin with "Good" and end in "Practice",
with the specific practice descriptor in between. GxP represents the
abbreviations of these titles, where x (a common symbol for a
variable) represents the specific descriptor.
40

G X P I N T R A N S P O R T A T I O N | C H A P T E R 2
The poor relations
Good Practice
GMP Production and Control of marketed
and investigational products
GSP Storage of pharmaceutical
products
GDP Distribution of pharmaceutical
products
GCP Clinical Trial Conduct
41

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP | A short history of how GMP evolved
Small Errors – Big Impact
January 1999 | Melsungen
The Company Braun Melsungen announces, that for their
injection solution product Glucose 5 Braun (10 ml Mini-Plasco)
Charge 7344C16, PZN: 2371769, Art.-Nr.: 02354543 a few
ampoules had been wrongly labelled. Those wrongly labelled
ampoules contain the API (Active Pharmaceutical Ingredient)
potassium chloride instead of glucose. The company requests
to check stocks and return any existing ampoules back to the
producer. The recall was initiated after two newborn babies
died of heart failure in Belgium.
“You cannot judge the Quality of a
Pharmaceutical Product by looking at it.”
42

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP | A short history of how GMP evolved
Small Errors – Big Impact
Contergan Scandal 1961/1962
• 2.000 children dead
• 10.000 children born with dysmelia
(malformation of limbs)
Suspected reason for this:
Pressing for market release prematurely,
before API had been thoroughly tested
43

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP | A short history of how GMP evolved
Pharmaceutical Development
Cost for Research and
Development of a new
medicine/pharmaceutical
product:
1.000.000.000+ EUR
Time span required from
the discovery of a new API
to the finished
pharmaceutical product:
10+ Years
Chances for succes
< 1%
44

G X P I N T R A N S P O R T A T I O N | C H A P T E R 1
Why GxP | A short history of how GMP evolved
Important Dates
1938 Food and Cosmetic Act (FD&C Act)
1962 Kefauver-Harris Drug Amendments
1968 WHO GMP Guideline
1978 21CFR 210/211 and 820
1983 First Guide to Computer Validation published by FDA
1987 Guideline on Process Validation published by FDA
1989 EC GMP-Guideline published
1990 ICH Programm initiated by EC Commission
1997 21CFR part 11 on electronic records and signatures
ICH Q7A (GMP for producers of APIs)
2005 New EC GMP Guideline published
ICH Q10 („Pharmaceutical Quality System“)
2008 updated cGMP Guide 21CFR 210/211
45

G X P I N T R A N S P O R T A T I O N | C H A P T E R 2
The poor
relations
GSP and GDP
enter the scene
46

G X P I N T R A N S P O R T A T I O N | C H A P T E R 2
The poor relations
What is Good Distribution
Practice (GDP)
“Good Distribution Practice (GDP)
is that part of quality assurance
which ensures that products are
consistently stored, transported and
handled under suitable conditions
as required by the marketing
authorisation (MA) 1 or product
specification.”
1
MA was previously known as a „product licence“
47

G X P I N T R A N S P O R T A T I O N | C H A P T E R 2
The poor relations
From the Introduction: WHO Technical Report No. 937
Annex 5 (2006) → 40 years on…
meanwhile superseded by No. 957 (2010)
“The quality of pharmaceutical products
can be affected by a lack of adequate
control over the numerous activities which
occur during the distribution process.”
Courier/Transport companies are therefore the (weakest?)
LINK in the supply chain between Manufacturer and point of
dispense/use
48

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
Poll Question
“Do you think it is
necessary to
qualify your
transportation
company and check
for GxP compliance?”
49

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting
Focus
Regulatory Updates
50

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
“Distribution is an important activity in the integrated
supply-chain management of pharmaceutical products.”
“The nature of risks involved is likely to be similar to that
for risks encountered in the Manufacturing environment.”
From the Introduction: WHO
Technical Report No. 957
Annex 5 (2010)
“Counterfeit pharmaceutical products are a real threat to
public health and safety. Consequently, it is essential to
protect the pharmaceutical supply chain against the
penetration of such products.”
“ Every activity in the distribution of pharmaceutical
products should be carried out according to the principles
of GMP, (…), GSP (…) and GDP (…). ”
51

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
1. Introduction
2. Scope of the document
3. Glossary
4. General Principles
5. Regulation of the distribution
of pharmaceutical products
6. Organisation and
Management
7. Personnel
8. Quality System
9. Premises, Warehousing and
Storage
10. Vehicles and Equipment
11. Shipment Containers and
Container labelling
12. Dispatch and Receipt
13. Transportation and Products
In Transit
14. Documentation
15. Repackaging and Relabelling
16. Complaints
17. Recalls
18. Returned Products
19. Counterfeit Pharmaceutical
Products
20. Importation
21. Contract Activities
22. Self-Inspection
Annex 5 (WHO Technical Report
Series No. 957, 2010)
Good distribution practices for
pharmaceutical products
(updated from WHO Technical
Report Series No. 937, 2006)
52

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
GDP adopted by PIC/S
Pharmaceutical Inspection Co-operation Scheme
Globalisation with longer and more complex supply chains but also counterfeiting problems have
been forcing pharmaceutical industry and inspectorates to challenge their current practices.
As a consequence, PIC/S has now amended its Pharmaceutical Inspection Co-operation Scheme Document
defining both Good Manufacturing Practice (GMP) and Good Distribution Practice (GDP) as core areas.
In the document it is now referred to Good Manufacturing and Distribution Practice (GMDP).
Changing over from GDP to GMDP does mean that PIC/S will now
also include GDP aspects in its co-operation, harmonisation and training activities.
(February 2012)
53

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
Regulatory Issues in the USA
U.S. Pharmacopeia 1079
“Good Storage and Shipping Practices”
21 CFR 210/211
‣“Current Good Manufacturing Practice in Manufacturing,
Processing, Packing or Holding of Drugs, General”
‣“cGMP for finished pharmaceuticals”
21 CFR 820
‣Quality System Regulations
‣Subpart E: Purchasing Controls -> Audits!
54

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
Regulatory Framework
EU > National Legislation
• Directive 2001/20/EC
• Directive 2003/294/EC
• Directive 2005/28/EC
• Decisions & Regulations
• Recommendations
• Ministry Decrees
• AMWH (Germany)
• AMBO 2009 (Austria)
• Pharma Authorities
55

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes
Original GDP Guideline 94/C 63/03 (1994):
Guidelines on Good Distribution Practice of Medicinal Products for Human Use
• General Guideline with less than 4 pages
• Legal Basis: Article 10 of Council Directive 92/25/EEC (31 March 1992)
Revised Draft of this Guideline published 15 July 2011
• Greatly expanded
• 10 Chapters, approx. 30 pages
• Legal Basis: Article 84 of Directive 2001/83/EC
• New Directive 2011/62/EU to fight Counterfeit Medication
• Current Status: revision for PUBLIC CONSULTATION ended 31 Dec 2011
56

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes
New GDP Guideline (draft)
1. Quality Management
QMS/Risk Mgt/Mgt Review/Change Control
2. Personnel
Responsibilities/Training/Hygiene
‣ Key Concept „Responsible Person“
similar to the QP function in GMP (Ch. 2.5)
3. Premises and Equipment
Handling/e-Systems/Qualification
4. Documentation
Signatures/Archiving/SOPs
5. Operations
Storage/Separation/Destruction
FEFO replaces FIFO
Ireland
Portugal
Spain
United
Kingdom
Belgium
Netherlands
France
Denmark
Germany
Luxembourg
Austria
Malta
Sweden
Slovenia
Czech
Republic
Italy
Poland
Hungary
Finland
Estonia
Latvia
Lithuania
Slovakia
Romania
Bulgaria
Greece
Cyprus
57

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes (continued)
New GDP Guideline (draft)
Finland
6. Complaints, Returns, Suspected Falsified Medicinal
Products and Medicinal Products Recalls
Training for Increased Awareness
7. Contract Operations
New Chapter/Qualification
8. Self-Inspections
New Requirement (3rd Party Audits allowed)
9. Transportation
24-hrs transit rule/Temp. Controlled transit rule
Training of Drivers
10. Specific Provisions for Brokers
New/Broker Activities defined
Ireland
Portugal
Spain
United
Kingdom
Belgium
Netherlands
France
Denmark
Germany
Luxembourg
Austria
Malta
Sweden
Slovenia
Czech
Republic
Italy
Poland
Hungary
Estonia
Latvia
Lithuania
Slovakia
Romania
Bulgaria
Greece
Cyprus
58

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes (continued)
Recent GMP updates for implementation 31 January 2013
Finland
Chapter 7 EU GMP Guideline revised
(Published 11 September 2012)
• Review and Control of all
Outsourced Activities (Risk based approach)
• Responsibility to assess
Legality, Suitability and Competence
of subcontractor
• Continuous assessment of
Quality and Performance
(identify and implement improvements)
-> Audits!
Ireland
Portugal
Spain
United
Kingdom
Belgium
Netherlands
France
• Review of Records and Results and Conformity of Services rendered.
Denmark
Germany
Luxembourg
Austria
Malta
Sweden
Slovenia
Czech
Republic
Italy
Poland
Hungary
Estonia
Latvia
Lithuania
Slovakia
Romania
Bulgaria
Greece
Cyprus
59

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes (continued)
Recent GMP updates for implementation 31 January 2013
Finland
Chapter 1 EU GMP Guideline revised
(Published 11 September 2012)
• Enhanced Requirements for a
Pharmaceutical Quality System
• Include other elements in addition to GMP:
- Management Review
- Continuous Improvement
- Quality Manual
Ireland
Spain
United
Kingdom
Belgium
Netherlands
France
Denmark
Germany
Luxembourg
Austria
Sweden
Slovenia
Czech
Republic
Italy
Poland
Hungary
Estonia
Latvia
Lithuania
Slovakia
Romania
Bulgaria
• Now a more
Holistic „Lifecycle“ Approach
-> ICH Q10
Portugal
Malta
Greece
Cyprus
60

G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
European Changes (continued)
EU GDP Guideline for APIs published on 11 February 2013
Status: Available for comments by stakeholders
Until 30 April 2013
• Wholesalers and Distributors are required
to maintain a Quality Sytem
• Requirements stipulated in 14 Chapters:
- Quality System
- Personnel
- Documentation
- Orders
- Procedures
- Records
- Premises and Equipment
- Receipt
- Storage
- Deliveries to Customers
- Transfer of Information
- Returns
- Complaints and Recalls
- Self-inspections
Ireland
Portugal
Spain
United
Kingdom
Belgium
Netherlands
France
Denmark
Germany
Luxembourg
Austria
Malta
Sweden
Slovenia
Czech
Republic
Italy
Poland
Hungary
Finland
Estonia
Latvia
Lithuania
Slovakia
Romania
Bulgaria
Greece
Cyprus
61

The Regulators – Status of current regulations
G X P I N T R A N S P O R T A T I O N | C H A P T E R 3
The shifting Focus
Consequences for Regulated
• Pharmaceutical Companies
• Must ensure that suppliers comply with
applicable regulations
• Audits
• Quality Agreements
• Subcontractors
• Courier/ Transport companies
• Airlines
62

G X P I N T R A N S P O R T A T I O N | C H A P T E R 4
Daily Distribution
Challenges
How to ask
the right Questions
63

G X P I N T R A N S P O R T A T I O N | C H A P T E R 4
Daily Distribution Challenges
Daily Distribution
Challenges
• New destinations
• Customs clearance issues
• Controlled drugs
• Cost savings and
environmental impact
• Regulatory considerations
64

G X P I N T R A N S P O R T A T I O N | C H A P T E R 4
Daily Distribution Challenges
Customs clearance/handling
• External Brokers
• Long clearance times
• Warehouse conditions
• Multiple handling agents in
the airline chain
65

G X P I N T R A N S P O R T A T I O N | C H A P T E R 4
Daily Distribution Challenges
• Complex supply chain
• Outsourcing
• Multiple & difficult countries/ availability of
proper infra-structure in each to ensure
efficient transit times
• Time zones/ availability
• Order & Release process
• Customs
• Intermediate storage
• Timelines
• Tamper-proof packaging
• Terror prevention / Cargo screening
• X-ray
• Timelines
66

G X P I N T R A N S P O R T A T I O N | C H A P T E R 4
Daily Distribution Challenges
Challenges – Summary
• New challenges –
New opportunities
• Regulatory considerations
• Transport and Infrastructure
• Temperature control
• Depot possibilities
67

G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential
Solutions
A Look at GxP
compliant services
68

G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Closing the Gap
Moving towards GxP compliance
• Quality Systems:
Processes and SOPs
• People:
Education/Training/
Experience
• Technology:
Packaging and Monitoring
69

G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Quality Systems
• Quality Management
• Set of policies, processes & procedures that enable the identification, measurement, control and
improvement of the storage and transportation of drug product
• Environment Management
• A section of the QMS that covers environmental controls, including an adequate organization
structure, roles & responsibilities, SOPs/policies/standards and processes for developing and
maintaining an environmental program
• Storage Management
• Program to provide continuous improvement in the storage of drug products with key locations in
buildings and facilities, vehicles and dispensing areas
• Transportation Management
• Provide continuous improvement of drug product lifecycle by better and more efficient use of
transportation processes
• Risk Management
Source: Mary Foster, USP Annual Meeting, Toronto, September
2009
70

G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
SOP # y-m-d SOP/Topics FAQ #
001 09-08-01 SOP Creation, Review + Distribution
002 10-01-01 Acceptance and Service Restrictions
003 10-01-01 Dangerous Goods - Shipping Restrictions
004 09-09-15 Fridges and Freezers for Pre-Conditioning of Gel Packs
005 09-09-15 Preparation of Gel Packs for Use
World Courier SOPs
(excerpt)
006 09-09-15
Selection and Use of Gel Packs within Temperature Controlled Shipment
Packaging
007 09-09-15 Dry Ice Information and Handling
008 09-08-01 Special Handcarry
–
009 09-08-01 Shipment Value/Currency + Weight/Dimensions
010 10-05-15 Handling of T2 Envirotainers
011 10-05-15 Handling of e1 Envirotainer
012 09-09-15 Dry Shipper Handling
013 09-11-16 GDP Compliant Documentation
014 09-11-16 Premises and Equipment
015 09-11-16 CAPA (Corrective And Preventive Action)
016 09-11-16 Change Control Management
017 09-11-16 External Audits
018 09-11-30 Self Inspection
019 09-11-16 Management of Outsourced Activities and Purchased Materials
020 09-11-30 Training Program
021 10-05-01
KPI and Incident Reporting Monitoring Process Performance and Product
Quality
022 09-11-30 Management Review Meeting
023 10-05-01 VIP TCS Cleaning Procedure
025 10-08-01 Internal Audits
030 09-09-01 Selecting and Preparing Temperature Monitors
031 09-09-01
032 10-05-17
Starting Temperature Monitors, Positioning Monitors inside Shipments and
Recording this Information
Recovering Temperature Monitors, Recovering and Distributing Data,
Storage of Used Monitors
032
127 Computer Backups and Disaster Recovery - see INET MIS
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
People
• Education
• Training
• Experience
• Test for Effectiveness
• Recurring Training
• Documentation
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Technology
Packaging and Monitoring
What are you looking for?
• Temperature
• Liquid nitrogen (-196°C)
• Dry ice (-80°C)
• Frozen (-25 to -10°C)
• Cold (2 to 8°C)
• Cool (8 to 15°C)
• Controlled Room Temperature CRT (15-25°C)
• Do not store/ ship over/ under XX°C
• ‘Ambient’
• Environment
• Weather, climate, season
• Transportation mode (plane, ship, train, truck)
• Accompanying products
• Transit time
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Packaging (Continued)
• Active systems
• Envirotainer/ Unicooler
• Temperature controlled trucks
• Passive systems
• Insulation
• Temperature control medium
• Single / Multiple use
• Environment
• Carbon Foot Print
• Size
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Temperature Monitoring
• Level of information
• Single/Multiple use
• Electronic/Paper
• Programming/Set up/Handling
• Assessment of data/Release decision
• Recipient vs. Shipper vs. Courier
• Data vs. Device
• Storage conditions vs. Transport conditions/Stability data
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Deviation Management
• There is no 100% safeguard against deviations
• Wrong configuration on data logger
• Data logger not started
• Transportation time > Monitoring time of data logger
• Shipment split at airport
• Outside qualified / validated transportation time
• Unexpected high / low ambient temperatures
• Temperature out of range
• Set up of Procedures in advance
• Key question: Quality relevant?
• YES: Individual assessment via Q function
• NO / Within specified acceptable deviation limits: Assessment via shipper,
recipient, courier, …
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Take Home Messages
• The first Regulations for GDP were established approximately
40 years after GMP evolved.
• The originating “mother document” for GDP regulations was
WHO Technical Report Series 937, Annex 5 (2006)
• This was revised into the new WHO
Technical Report Series 957, Annex 5 (2010)
• It is expected that the shifted focus of this new document will be
taken up by various Regulatory Bodies across the globe.
New EU GDP Guidelines awaiting implememtation
New Legislation expected in EU and associated countries
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G X P I N T R A N S P O R T A T I O N | C H A P T E R 5
Potential Solutions
Take Home Messages
• GxP compliance is in focus and will be enforced by Authorities
• GxP guidelines are applicable for ALL involved in supply chain
(including Courier/Transportation)
• Biopharm Companies must comply with a wide and far reaching
set of rules and regulations
• GxP standards require service partner qualification and written
Quality Agreements in which responsibilities are clearly defined
• There is no universal international standard:
The rules are different in different parts of the world
To close the gap, you need:
QUALITY SYSTEMS, PEOPLE & TECHNOLOGY
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Thank you for your attention.
Michael Fleischer
Regional Quality Coordinator NCEE
GMP Compliance & QA Manager
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