Shipping validation, from customer

prospective
Sharon Yarkoni
08, March 2016

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Agenda
 Good Distribution Practice the three main streams.
 USP 1079,1197, 1083
 PDA 39, 46, 52, 53,72
 Regulatory bodies requirements.
 Risks involved in shipping and distribution
 Risks involved during transportation.
 Case study.

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cGDP – is based of 3 main streams:

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Chapter <1079> Outline
Good Storage & Distribution Practices for
Drug Products.

 Introduction, Definitions, Scope

 Background Information

 Responsibilities

 Labeling Information

 Quality Management System

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Chapter <1197> Outline
Good Distribution Practices for
Pharmaceutical excipients.

 Quality Organization & Documentation

 Premises, Storage, Repackaging & Stability

 Returned Goods, Dispatch, Transport, Importation,

Traceability

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Chapter <1083> Outline

Good Distribution Practices – Supply Chain

Integrity

 Importation, Supply Chain Risk Management, Effective Supplier

Partnerships, Supply Chain Quality System

 Counterfeit Drugs & Medical Devices

 Best Practices to Combat Counterfeit Drugs & Medical

Devices

 Theft

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 Summary of <1079>, <1083> &
<1197>

Chapter Coverage QMS Environmental Importation Counterfeit Traceability

Control

<1079> DP Yes Yes No No No

<1083> EXCP; DS; DP; Yes No Yes Yes Yes

MD

<1197> EXCP Yes Yes Yes Yes Yes

EXCP = Excipients; DS = Drug Substance; DP = Drug Products

MD = Medical Devices

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 Regulatory Guidance- EU GDP
 Article 84 of Directive 2001/83/EC on the
Community code relating to medicinal products for
human use is under revision for public consultation
 Reason: 1994 GDP no longer adequate

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Regulatory Guidance-Mexico Ministry of
Health (MOH)

 “The cold chain report must correspond to the

temperature of the product, not to the external one.”
 Mexican MOH “COFEPRIS” only allows use of data
loggers they do not allow use of electronic or chemical
indicators

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Process- PDA Technical Reports
 PDA TR 39 (revised 2007) Guidance for Temperature-
Controlled Medicinal Products: Maintaining the Quality of
Sensitive Medicinal Products Through the Transportation
Environment.

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Process- PDA Technical Reports
 PDA TR 46 Last Mile: Guidance for Good Distribution
Practices for Pharmaceutical Products to the End User.

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Process- PDA Technical Reports
 PDA TR 52 Guidance for Good Distribution Practices
(GDPs) for the Pharmaceutical Supply Chain.

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Process- PDA Technical Reports
 PDA TR 53 Guidance for Industry: Stability Testing to
Support Distribution of New Drug Products.

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Standards
 IATA INFORMATION NOTICE: time and temperature
sensitive label to become mandatory 1 July 2012.

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Transport process involves:
Variance ambient temperature.

Modes of transportation.

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Shipping systems

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Temperature monitoring devices

There are different types of data loggers for different temperature

conditions such as 2-8°C, -30°C, RT etc.

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Cooling material

Dry ICE- changes from a solid to a gas at −78.5 °C

Ice Packs-can be pre cooled to 2-8 °C, -30 °C

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Transport process involves:

Transit duration (since the product left production site until it gets to the
final costumer).

Route (where do I send my product, how many stops on the way).

Material handling (temperature sensitive products, light sensitive etc.)

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Risks during storage and distribution

 Mix up of products
 Mix up of batches
 Contamination
 High temperature/high humidity
 Light
 Freezing
 Pests
 Distribution of non released products
 Using of inappropriate vehicles
 Damage to product

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Risks during Transportation

 Shipment of wrong product

 Shipment to wrong destination
 Inappropriate handling/loading
 Damage in transit
 Loss in transit
 Temperature deviation
 Mixing of batches
 Breakdown of pallets
 Late delivery

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Qualification versus Validation

Qualification- documented testing that demonstrate with a high degree of

assurance that a specific process will meet its pre determined acceptance
criteria.

Validation- documented testing performed under highly controlled conditions

that demonstrates that a process consistently produces a result meeting
pre determent acceptance criteria.

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Shipping Qualification

Physical
Challenge

Shipping
Qualification
Packaging
Integrity Thermal
Tests Study

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 Case study- protocol

Maximum load-

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 Case study- protocol
Minimum load-

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 Case study- protocol

Pallet configuration

Maximum Load Minimum Load

shipping carton shipping carton

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 Case study- protocol

Specifications:

For the duration of the shipment the temperature in direct vicinity of the
product should not exceed -20ºC. Temperature limitations to the air
temperatures outside the shipper are not specified.

The maximum duration for the complete shipment is not to exceed 72hours.
The expected average duration of an individual shipment is 36 hours.

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 Case study- report

Executive summary:

A series of 12 shipments were carried out

Each shipment included Maximum and Minimum configuration

Different vial formats (5 ml and 1or 2 ml ) were investigated separately

The recorded data was compared to data available from summer shipments
of 2008, 2009

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 Case study- report

The complete cold chain consist of total of 8 legs:

Packaging and storage at manufacturer

Road transport manufacturer to Ben gurion Airport

Freight handling at Tel Aviv airport

Air transport Tel Aviv to Frankfurt

Freight handling at Frankfurt airport

Air transport Frankfurt to Memphis

Freight handling at Memphis airport

Road transport Memphis airport to Distribution warehouse

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 Case study- report

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 Case study- report
Ambient temperature (summer profile):

Leg Temperature duration

measured
Packaging and storage at Mfr 11°C to 23°C 16-18
Road transport Mfr to BGA 3°C to 27°C 0.5-1.5

Freight handling at BGA Controlled area 1.5-4

Air transport BGA-Frankfurt -15°C to 18°C 5-6.5

Freight handling at Frankfurt airport -10°C to 12°C 1.5-2

Air transport Frankfurt to Memphis -19°C to 20°C 10-12

Freight handling at Memphis airport 0°C to 20°C 6.5-32.5

Road transport Memphis airport to -1°C to 25°C 0.5-5

31 Distribution warehouse
 Case study- report

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 Case study- report
Historic Data:
Series of 30 shipments from summer 2008-2009 were analyzed

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 Case study- report
Historic Data:
Series of 30 shipments from summer 2008-2009 were analyzed

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 Case study- report

Conclusions and recommendations:

Temperature is fully within range during the entire shipment (both minimum
and maximum).

The shipping configuration selected for the minimum and maximum load in
this study meets the defined temperature specification.

All collected data in this study as well as the historical data analyzed is fully
compatible with the requirements.

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 Case study- report
The maximum shipping period of 72 hours can be exceeded by one hour
without undue thermal risk to the product.

The most critical phase in the transport length is fount at the Memphis
airport (the product was held for 6-32 hours prior to release, probably
customs release).

The location chosen for the data logger needs to be at the side wall on the
upper level in order to measure the most critical temperature during the
shipment.

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 Case study- Physical challenge

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 Case study- Physical challenge

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 Case study- Physical challenge

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 Case study- Physical challenge

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 Stability & Packaging Integrity

Stability indicating test methods

Performed after each thermal study to ensure that the shipment didn’t
impact the quality of the product.

Specific protocol was prepared to determine the tests to be performed

Package Integrity

Visual Inspection performed to ensure that the shipment didn't impact the
product.

Sterility test performed to ensure that the shipment didn't impact the
integrity of the product.

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 Thank You!
[email protected]
0502071733
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