Shipping validation, from customer

prospective

Sharon Yarkoni

08, March 2016

1

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.

2

cGDP – is based of 3 main streams:

3

Chapter Outline

Good Storage & Distribution Practices for

Drug Products.

Introduction, Definitions, Scope

Background Information

Responsibilities

Labeling Information

Quality Management System

4

Chapter Outline

Good Distribution Practices for

Pharmaceutical excipients.

Quality Organization & Documentation

Premises, Storage, Repackaging & Stability

Returned Goods, Dispatch, Transport, Importation,

Traceability

5

Chapter 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

6

Summary of , &

Chapter

Coverage

QMS

Environmental

Control

Importation

Counterfeit

Traceability

DP

Yes

Yes

No

No

No

EXCP; DS; DP;

MD

Yes

No

Yes

Yes

Yes

EXCP

Yes

Yes

Yes

Yes

Yes

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

MD = Medical Devices

7

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

8

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

9

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.

10

Process- PDA Technical Reports

PDA TR 46 Last Mile: Guidance for Good Distribution

Practices for Pharmaceutical Products to the End User.

11

Process- PDA Technical Reports

PDA TR 52 Guidance for Good Distribution Practices

(GDPs) for the Pharmaceutical Supply Chain.

12

Process- PDA Technical Reports

PDA TR 53 Guidance for Industry: Stability Testing to

Support Distribution of New Drug Products.

13

Standards

IATA INFORMATION NOTICE: time and temperature

sensitive label to become mandatory 1 July 2012.

14

Transport process involves:

Variance ambient temperature.

Modes of transportation.

15

Shipping systems

16

Temperature monitoring devices

There are different types of data loggers for different temperature

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

17

http://www.rfidjournal.com/imagecatalogue/imageview/2672/?RefererURL=/article/view/1977/1

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

18

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.)

19

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

20

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

21

Qualification versus Validation

high degree of documented testing that demonstrate with a -Qualification

that a specific process will meet its pre determined acceptance assurance

criteria.

Validation- documented testing performed under highly controlled conditions

produces a result meeting consistentlythat demonstrates that a process

pre determent acceptance criteria.

22

Shipping Qualification

23

Shipping Qualification

Physical

Challenge

Thermal Study

Packaging Integrity

Tests

Case study- protocol

Maximum load-

24

Case study- protocol

Minimum load-

25

Case study- protocol

Pallet configuration

Minimum Load shipping carton

Maximum Load shipping carton

26

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.

27

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

28

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

29

Case study- report

30

Case study- report Ambient temperature (summer profile):

duration Temperature

measured

Leg

16-18 11°C to 23°C Packaging and storage at Mfr

0.5-1.5 3°C to 27°C

Road transport Mfr to BGA

1.5-4 Controlled area Freight handling at BGA

5-6.5 -15°C to 18°C

Air transport BGA-Frankfurt

1.5-2 -10°C to 12°C

Freight handling at Frankfurt airport

10-12 -19°C to 20°C

Air transport Frankfurt to Memphis

6.5-32.5 0°C to 20°C

Freight handling at Memphis airport

0.5-5 -1°C to 25°C

Road transport Memphis airport to

Distribution warehouse 31

Case study- report

32

Case study- report

Historic Data:

Series of 30 shipments from summer 2008-2009 were analyzed

33

Case study- report

Historic Data:

Series of 30 shipments from summer 2008-2009 were analyzed

34

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.

35

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.

36

Case study- Physical challenge

37

Case study- Physical challenge

38

Case study- Physical challenge

39

Case study- Physical challenge

40

Stability & Packaging Integrity

41

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.

42

Thank You!

Sharkoni@gmail.com

0502071733

mailto:Sharony@gmail.com