1

How to Validate Temperatures Within the Supply Chain

Pharmaceutical and Personal Care Logistics Association

PPCLA

PPCLA

2Agenda• Introduction• Standards and Regulations• 1) Validation process

• Protocol• Packaging design• Testing

• 2) Trailer validation• Variables• Health Canada / Guide 0069

PPCLA

3About Us:• Third party material test laboratory• Staff includes 2 MSc. Chemists, 1 mechanical

Engineer, lab technicians.• 11 000 sq. feet test facility.• Involved in cold Chain validation for the

Pharmaceutical Industry since 2001.• CGMP Adherence• Approved Laboratory for various types of transit

test services (ISTA, NCC, Transport Canada/HAZMAT).• CGSB approved Laboratory for various tests• Bombardier approved test laboratory (Mass Transit,

Recreational)• Health Canada / Hazardous Product Act

PPCLA

4The Chain

5

How to Validate Temperatures Within the Supply Chain

Documenting through testing and monitoring that we are in control of our logistics process from a temperature standpoint.

PPCLA

PPCLA

6

Current Standards and Regulations:

• Health Canada, guide 0069 (nov. 2005)

• USP 1079 (June 2005)• ASTM D-3103-99 (1999)• ISTA 5B• ISTA 7D• Transport Canada / Hazmat

PPCLA

7

Health canada, guide 0069• Applies also to clinical trial drugs and promotional samples

• 1.2 Warehousing & Storage vs. packaging• « Monitoring …temperature mapping ».

• 2.1  « The transport process and containers should prevent damage and maintain the integrity and quality of the drug product ».

PPCLA

8

ASTM D-3103-99 Standard Test Method for Thermal Insulation Quality of Packages.

• Widely called up in various test protocols for cold chain validation

• Needs to be tightened up for:- Thermocouple tolerance- Environmental chamber tolerances- Number of data points required

• Revision currently in the works

PPCLA

9ISTA - Mission

Provide economical and environmental benefits by preventing product damage and over packaging during the physical distribution of products as a result of creating, advocating and providing performance testing standards, training, education and certification.

PPCLA

10

International Safe Transit Association

• Simulate shipping hazards• Based on ASTM procedures• Added pass/fail criteria

• Mass• Shape• Dimensions• Logistics

PPCLA

11ISTA 5 B• 5B - Focused Simulation Guide for Thermal Performance testing of temperature controlled transport packaging.- References ASTM D-3103- Good starting point for developing a test protocol for cold chain validation including how to create the temperature profile. - Requirements need to be tightened up.

PPCLA

12ISTA 7D

• Complete test sequence including actual temperature cycling combined with mechanical testing to simulate shipping hazards

PPCLA

13

ISTA 7 D – test sequence

PPCLA

14

Validation Protocol Development (1)

Purpose Objectives Definitions, reference documents Equipment/Product requirements Testing procedure

PPCLA

15

Validation Protocol Development (2)

PurposeTo establish documented evidence that the shipping containers used provide an adequate State of Control.

Packaging Trailer Refrigerator Warehouse

PPCLA

16

Validation Protocol Development (3)

Objectives. Test pack outs under controlled conditions simulating foreseeable temperature extremes seen in “real world”.

To have proper documentation for operating, maintaining, and/or repeating any part of the testing performed.

To have proper documentation for packing the product according to a successful pack out scheme.

Verify that packaging maintains product within acceptable temperature limits under specified shipping conditions.

PPCLA

17

Validation Protocol Development (4)

Definitions, reference documentsTerminology used within protocol (#3 box, -10 pcm)

Test methods and SOPs Equipment/Product requirements

materials required to complete the testing

Packaging, icing, dunnage… Pack out assembly instructions

Test equipment (chamber, data logger…)

PPCLA

18

Equipment requirements example:1. Gel Conditionning Freezer

Inventory # MI-EQ-087 Manufacturer: So-Low Model: A18-120, Serial# 91928/37 Controller: Fenwal model 400 Type T 20AWG thermocouple Inventory # MI-EQ-

223 Digital temperature reader Inventory # MI-EQ-204 Manufacturer: Fluke Model 714, Serial # 7013190

Validation Protocol Development (5)

PPCLA

19

Validation Protocol Development (6)

Test Equipment Calibration Temperatures profiles

• Winter, summer, fall/spring• Sources

• Public databases• Courier databases• Actual shipment monitoring

Packaging configurations/thermocouple placement

Pack out must reflect actual practice

Test Procedure:

PPCLA

20Packaging design (1): Know your product

Physical properties Temperature stability Allowable excursions Quantities shipped per day, weeks Min/max loads

PPCLA

21Packaging design (2):

Know your shipping environment: Road, air, vibration Shipment duration Extreme ambient temperature during each segment of the shipping route

PPCLA

22Packaging design (3):• Protective / secondary container

Insulating container Payload configuration Inserts Dunnage (very important) Temperature monitor Icing

Type (Ice, Gel, PCM, Dry Ice) Location, combination

PPCLA

23Cooling curves

PPCLA

24

Carton Tray5 requ.

Notes: 1. Provide Air Bag dunnage as required to stabilize load.2. Provide corrugated sheets between PCM’s and product. (3 required)3. Representative Products tested: ABC45

AIR BAGSSee note 1

PCM 18 OZ. FROZEN

Shown in blue (4 REQU.)

INSULATEDSHIPPER

CORRUGATEDPADS See note 2

LID

PCM 18 OZ. REFRIGERATED

Shown green (16 REQU.)

Outside of Liner

Validation test package configuration

Courtesy of Joe Villa, Thermal Packaging Solutions

PPCLA

25

Validation testing (1):

Sample reception Sample conditioning Equipment

Walk in chamber (Thermal mapping +/- 0,5 C)

Temperature data-logger; pre and post-test calibration (+/- 0,5 C)

Calibration NIST traceable

PPCLA

26

Box Gel # 6 - Maximum Load

-15

-13

-11

-9

-7

-5

-3

-1

1

3

5

7

9

11

13

15

17

19

21

23

25

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39

Time (h)

Tem

pera

ture

(°C

)temp_81 temp_82 temp_83 temp_84 temp_85 temp_86 temp_87 temp_88 temp_89 temp_90temp_91 temp_92 temp_93 temp_94 temp_95 temp_96 temp_97 temp_98 temp_107 temp_108

START END

PPCLA

27

Pre-validated containers

Cold chain validation is geared toward your product as a function of:The product physical & chemical characteristics

Shipping logistics Ambient temperature Duration Transport mode

Temperature controlledQuantities shipped

In vial In box Pallet

PPCLA

28Trailer validation (1)

PPCLA

29

Trailer validation – Caracteristics (2)

• Temperature stratification• Ambient temperature• Wind• Truck speed• Sunlight• Longitudinal shape• Defrost cycle• Vibrations

PPCLA

30

Trailer Validation – Guide 0069 (3)

• Section 1:• Well maintained.• Free from frost build up.• Adequate air distribution.• Loading configurations should allow efficient air distribution.

• Multipoint temperature monitoring and alarms at points representing temperature extremes.

PPCLA

31

Trailer Validation – Guide 0069 (4)

• Section 2:• Needs to be validated for proper temperature range (2.4).

• Needs to be mapped and monitored only if it provides the primary means for environmental control