Warehouse Mapping Process Best Practices for Warehouse es ... · ISPE Good Practice Guide – Cold Chain Management (2011). Irish Medicines Board Guide to Control and Monitoring of

Warehouse

Mapping

Processes Best Practices for Warehouse

Temperature Management and

Control

This guide does not purport to be an interpretation of law and/or regulations and is for guidance purposes only.

© Cryopak 2015 2

This guide does not purport to be an interpretation of law and/or regulations and is for guidance purposes

only.

PUBLISHED BY:

This material is subject to copyright protection, with all copyrights retained by Cryopak and its individual

partners. All rights reserved. The reproduction, transfer, distribution or storage of information contained in

this document in any form without the prior written consent of Cryopak is strictly prohibited. All

specifications — technical included — are subject to change without notice.

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© Cryopak 2015 3

Contents

1. AUTHOR & CONTRIBUTORS ........................................................................................ 4

2. ABBREVIATION & DEFINITION .................................................................................. 5

3. SCOPE ................................................................................................................................... 7

4. PROJECT REQUIREMENTS ............................................................................................ 8

5. PROCESS .............................................................................................................................. 9

5.1. Step 1 – Protocol Writing ............................................................................................... 9

5.1.1. Choosing the Perfect Moment ............................................................................ 9

5.1.2. Data Logger Distribution ..................................................................................... 9

5.1.3. Study Duration .................................................................................................... 12

5.1.4. Measuring Range ................................................................................................ 13

5.1.5. Testing .................................................................................................................. 13

5.2. Step 2 – Protocol Execution .......................................................................................... 14

5.2.1. Programming Data Loggers .............................................................................. 14

5.2.2. Installing Data Loggers ...................................................................................... 15

5.2.3. Documentation .................................................................................................... 15

5.2.4. Removing Data Loggers .................................................................................... 15

5.3. Step 3 – Report .............................................................................................................. 16

5.3.1. Data Compilation ............................................................................................... 16

5.3.2. Mean Kinetic Temperature (MKT) ................................................................... 16

5.3.3. Calibration and Post-Calibration Requirements ............................................ 17

5.3.4. Data Analysis ...................................................................................................... 17

6. CONCLUSION .................................................................................................................. 19

7. REFERENCES ..................................................................................................................... 20


© Cryopak 2015 4

1. AUTHOR & CONTRIBUTORS

Jalal Belbal, B.Sc. (eng.) – Main Author

Jalal Belbal, Validation & Regulatory Compliance Manager at Cryopak, has 10 years of experience

in the pharmaceutical, biotechnology, and life science industries. He has worked on a wide range

of qualification projects including mapping process, laboratory equipment, packaging and

software validation to help the Life Science industry fulfill US and Canadian regulatory

requirements and best practices, such as the Guide 0069, PIC/s-Annex11, PDA – Technical Report

No.64, USP 36 Chapter <1079>, GAMP and FDA’s 21 CFR Parts 11, 210, 211, and 820.

Jalal Belbal earned a bachelor’s degree in Biochemistry & Environmental Engineering from

University Laval, Quebec.

Benoît Chedhomme - Contributor

Benoît Chedhomme, Sales Manager – Canada at Cryopak, has over 10 years of experience in the

pharmaceutical, biotechnology and life science industries. After immigrating to Canada in 2004,

he joined Alternatives Technologie Pharma, a start-up company that grew to become a recognized

national cold chain solution provider. Over the years, Benoît has helped many CRO/CMO, 3PL

and pharmaceutical wholesalers to comply with regulatory requirements and optimize their cold

chain process.

Benoît Chedhomme earned a master’s degree in Sales & Distribution Network from University of

Montpellier, France.

Geneviève Joseph – Contributor

Geneviève Joseph, Marketing Coordinator at Cryopak, has over 10 years of experience in retail

sales & customer service. She joined Alternatives Technologie Pharma in 2012 as a documentation

specialist, where she gained experience in mapping process and thermal equipment qualification.

She joined the Sales & marketing team at Cryopak, its sister company, a year later.

Geneviève Joseph earned a degree in Political Science and a certificate in Professional Writing from

University of Montreal, Quebec. She is currently a McGill University student in Marketing.


© Cryopak 2015 5

2. ABBREVIATION & DEFINITION

In order to aid the understanding of terms and acronyms used in this document, a brief technical

definition is shown below.

Please note: This document only refers to temperature mapping. This service is also available for

relative humidity.

Terms / Acronyms Definitions

HC Health Canada

HVAC Heating, Ventilation, and Air Conditioning

HPRA Health Product Regulatory Authority

EMA European Medicines Agency

USP U.S Pharmacopeia

GMP Good Manufacturing Practice

PDA Parenteral Drug Association

PIC/S Pharmaceutical Inspection Co-operation Scheme

WHO World Health Organization

FDA Food and Drugs Administration

ISPE International Society For Pharmaceutical Engineering

ICH Internal Conference on Harmonisation

GDP Good Distribution Practice

MKT Mean Kinetic Temperature

EMS Environmental Monitoring System

21 CFR Code of Federal Regulation, number 21 from Food and Drug

Administration (FDA)

NIST National Institute of Standards and Technology

NCRC National Calibration Reference Centre

SOP Standard Operating Procedure

Software

Software is a generic term for organized collections of computer data and

instructions, often broken into two major categories: system software that

provides the basic non-task-specific functions of the computer, and

application software which is used by users to accomplish specific tasks.


© Cryopak 2015 6

Terms / Acronyms Definitions

Data logger

An electronic device that records data over time or in relation to location

either with a built-in instrument or sensor, or via external instruments and

sensors. Increasingly, but not entirely, they are based on a digital processor

(or computer). They generally are small, battery powered, portable, and

equipped with a microprocessor, internal memory for data storage, and

sensors. Some data loggers interface with a personal computer and utilize

software to activate the data logger and view and analyze the collected data,

while others have a local interface device (keypad, LCD) and can be used as

a stand-alone device.

Pharmaceutical products

Any product intended for human use or veterinary product intended for

administration to food production animals, presented in its finished dosage

form that is subject to control by pharmaceutical legislation in either the

exporting or the importing state and includes products for which a

prescription is required, products which may be sold to patients without a

prescription, biologicals and vaccines. Medical devices are not included.

Protocol

A predefined, written procedural method for the design and

implementation of experiments to define and document the methodology

and criteria required to assess the capability of a temperature and/or

relative humidity controlled system to achieve the desired results.

Protocol deviation

A deviation that occurs when a result is unexpected (i.e. fails to meet the

predetermined acceptance criteria) or a procedure in the protocol cannot be

executed as written (e.g., when a challenge is met using a methodology

other than that described in the protocol or a process).

Set point

The specific temperature programmed by the user into the temperature

controller unit that establishes the target temperature in the controlled

environmental space.

CAPA

Corrective Action and Preventive Action

Corrective Action: Action to eliminate the cause of a detected

nonconformity or other undesirable situation.

Preventive Action: Action to eliminate the cause of a potential

nonconformity or other undesirable potential situation.

Seasonal Mapping Validation procedure performed during a particular time of year; mapping

study done twice, once in winter, once in summer.

Temperature Stratification

Thermal stratification; feature of gasses and liquids in which high energy

molecules move to the top of a contained space, and cooler molecules move

to the bottom; layering of differing temperatures from the floor of the

facility to the ceiling.

http://en.wikipedia.org/wiki/Scientific_instrument

http://en.wikipedia.org/wiki/Sensor


© Cryopak 2015 7

3. SCOPE

A mapping study is performed to generate a temperature profile

of the facility, in order to ensure it maintains the temperature

range required by the specific products. Temperature mapping

studies help manufacturers, distributors and transporters of

pharmaceutical, biotechnology and other temperature sensitive

products protect their value by identifying potential

environmental control problems before products are affected, as

inadequately controlled environments can lead to ineffective

and spoiled products. It’s also an essential exercise to determine

the location of the real-time monitoring system sensors..

Fundamental to any controlled process is the expectation that

pharmaceutical and other products that are stored and shipped

within a controlled environment are maintained within their

defined range, as all drugs should be stored according to the

conditions described on the label.

The temperature within an environmentally controlled

warehouse is expected to be maintained1:

Reliably and consistently through the entire period the

product is stored within the controlled environment;

In compliance with the product requirements for

temperature at all locations in which the product might

be stored (i.e. temperature and location/storage

boundary).

The recent changes in the FDA and Canadian regulations (GUI-

0069 and various federal CFR codes), along with the objective to eliminate the waste of time and

money to fix environmental conditions failures has made temperature mapping an integral aspect

of any storage area operation.

1 PARENTERAL DRUG ASSOCIATION. Technical Report No.64 – Active Temperature Controlled

Systems: Qualification Guidance, PDA, 2013, 58p.

“Temperatures should be

controlled and monitored

using calibrated

monitoring devices and

records of temperature

and alarms, where

applicable, should be

maintained. Monitoring

of storage facilities is

conducted at points

representing the worst

case scenarios of the

temperature range based

on temperature

mapping.”

- Guidelines for

Temperature

Control of Drug

Products during

Storage and

Transportation –

GUI-0069

Health

Canada

REGULATORY REQUIREMENTS


© Cryopak 2015 8

4. PROJECT REQUIREMENTS

Regulatory authorities underline the importance of storage and transportation temperature in

maintaining drugs and temperature sensitive products’ quality within distribution network.

Temperature mapping is required to assess the ability of the facility to maintain its required

temperature range.

Canada United Sates Worldwide Others

Health Canada

Guidelines for Temperature Control of Drug Products during Storage and Transportation (GUI-0069)

Food and Drug Regulation, Section C.02.015.

PIC/S

Guide to Good Manufacturing Practice for Medicinal Products Annex.

USP 36

USP General Chapter <1079˃ Good Storage And Shipping Practices

USP General Chapter <1083˃ Good Distribution Practices-Supply Chain Integrity.

FDA

CFR Part 820.150 Storage

CFR 21 Guidance for Industry Part 11, Electronic Records, Electronic Signatures Scope and Application.

WHO

Good Distribution Practices for Pharmaceutical Products TRS No.957.Annex 5 (2010)

Model requirements for the storage and transport of time and temperature sensitive pharmaceutical products TRS No.961, Annex 9 (2011).

PDA

PDA Technical Report No. 64- Active Temperature Controlled Systems: Qualification Guidance.

Technical Report 58- Risk Management for Temperature Controlled Distribution.

ICH

Guidance for Industry Q1A (R2) Stability Testing of New Drug Substances and Products.

ISPE

Good Practice Guide – Cold Chain Management (2011).

Irish Medicines Board

Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medical Products and Active Substances.

EMA (Europe)

(2013/C 68/01) Good Distribution Practice of Medicinal Products for Human Use.

HPRA

Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medicinal Products and Active Substances.

Figure 1: Regulations and Guidelines around the World

The standards set forth in the Good Distribution Practice (GDP) guidelines provide the framework

for conducting mapping studies. Temperature mapping studies are expected to collect the

following information2:

Ensure the facility meets pharmaceutical industry specific regulatory requirements;

Identify potential hot spots and cold spots within the facility to ensure products

remain within temperature range at all time;

The impact of physical interventions (door openings, HVAC, power failures, etc.);

Temperature variations across the area;

Temperature variations at specific locations;

Duration of any potential temperature excursions;

2 (2013/C 68/01) Good Distribution Practice of Medicinal Products for Human Use


© Cryopak 2015 9

Identify and eliminate potential weaknesses or failures in the cold chain process;

Identify any machinery that might generate heat in the warehouse;

Protect and ensure the products quality that are manufactured and distributed;

Optimise the use of space and energy within individual storage facilities.

As regulators increase their emphasis on GMP requirements, the definitive method to demonstrate

that all controlled storage equipment, or storage areas, stay within the specified limits is through a

thorough temperature mapping study.

5. PROCESS

Proper organization and documentation are critical to maintaining compliance and consistency.

Cryopak’s regulatory compliance experts strongly recommend the following 3 step approach:

5.1. Step 1 – Protocol Writing

The protocol is a comprehensive document used to guide the executants through the verification

of the temperature distribution within the warehouse during worst case scenarios, which are

usually at the coldest and warmest extremes of the winter and summer seasons. This detailed

protocol should include a few elements that are detailed below.

5.1.1. Choosing the Perfect Moment

Choosing the perfect timing is an art our regulatory compliance experts have mastered over the

years. Temperature mapping should be performed during the coldest week of the winter season

and the warmest week of the summer season for all storage areas to ensure that they are likely to

remain within the specified temperature limits at all time through the year. These seasons are

chosen as extreme temperatures are more likely to adversely affect the temperature distribution

within the storage area.

Although it is strongly recommended to map the storage area when empty and loaded to get a

better understanding of the temperature distribution, it is almost impossible to do so for practical

reasons. However, customers opening a new facility or moving in a new building will likely

perform an empty mapping in order to get their license from the authorities.

5.1.2. Data Logger Distribution

There are no standards or set formulas for the number or placement of data loggers that should be

used for a mapping study. However, your study must demonstrate 3-dimensional uniformity and

compliance with your product requirements. These multiple data points account for gradients or


© Cryopak 2015 10

temperature extremes in critical areas where product will be stored. Good practice is to use a

sufficient number to understand the environment, but not more than needed. Not enough sensors

cannot justify the results; too many means handling more data than necessary.

You should set the number of data loggers to use according to the warehouse volume.

When determining sensor location, you need to identify areas where unacceptable temperature

variations may affect the products’ quality. Large and open spaces are more difficult to maintain

at a consistent temperature. Make sure to install data loggers at all potentially problematic and

critical locations3:

Temperature gradients between the cooler floor and warmer air at the ceiling: as

heated air rises, make sure to measure any temperature stratification in larger spaces;

HVAC system’s capacity to move air, as well as the sizing of blowers or fans to

adequately circulate air: poor airflow or a bad fan location can cause extreme

temperature near sources of heat or cold, such as HVAC ducts or windows;

Layout of racks, shelves, pallets and other surfaces where products will potentially be

stored: racking and shelving configurations may create hot spots by obstructing the

airflow.

Close to the controllers;

Doors, windows and other risky areas, including outside walls that may respond to

external temperatures: doors or exits left open to regulate the overall temperature will

affect the environmental conditions around nearby racks;

Effect of incidences like power failures and vulnerable areas where there may be wide

variations in temperature, such as shipping doors;

Areas that are non-shelved, but deemed to be used as interim storage areas before

placing on racking;

Measure the external temperature during the study by installing one data logger

outside.

3 ROBEY, Sarah. Our blog Whichwarehouse, [http://www.whichwarehouse.com/blog/news/tips-pharma-storage-speciality-warehouse-storage-warehouse-space/] (page consulted on April 14th, 2015)


© Cryopak 2015 11

Using a 3-dimensional temperature profile means installing data loggers on at least three planes –

top to bottom, left to right and front to back (see figure 2), or on three (3) rows in height

(approximately at 6 feet, 12 feet and 18 feet high) where high racking exists. Additional data loggers

should be added where known cool or warm areas exist. No matter which option you choose, make

sure to use a consistent rationale for data loggers’ distribution.

Figure 2: Example of Data Loggers Location

For a larger warehouse, a justification of a 30 to 60-meter distance between data loggers could be

used with additional data loggers in vulnerable areas. These areas include loading docks, solar

heating from windows, heat generated from artificial lights, air circulation and uneven building

insulation. To ensure even data logger distribution, it is recommended to divide the warehouse

into smaller sections (see figure 3).

Figure 3: Warehouse overview: different sections


© Cryopak 2015 12

Be sure to document the location of every data logger and label it to ensure that it is installed at the

right location during execution (see figure 4).

Figure 4: Documenting and labeling data loggers

5.1.3. Study Duration

The duration of the mapping study is also a key factor to create a meaningful set of data. The total

duration must capture enough of the system’s operation to justify consistent and repeatable

operation. The study must also attempt to capture events that could be considered “worst-case”

conditions of the temperature range based on temperature mapping.

Initial mapping of an empty warehouse can be performed over a 3-day (72 hour) period, during

summer and winter seasons. If you are already operating, you may want to extend the mapping

period from 7 days to two weeks (14 days) during summer and winter seasons, in order to capture

the normal differences in schedule through the workweek4 and “to have a sufficient time frame to

capture workflow variation that may impact air flow and the resulting temperature fluctuation”5.

4 USP General Chapter <1079> Good Storage and Shipping Practices, USP 28, Suppl. 2, August 1st, 2015. 5 WILLIAMSON, Mike. Mike Williamson Validation Blog, [www.mikewilliamsonvalidation.wordpress.com/ 2013/01/02/qualifying-controlled-warehouse-space/] (page consulted on April 14th, 2015)


© Cryopak 2015 13

5.1.4. Measuring Range

Storage conditions for pharmaceutical products and materials should be in compliance with the

product labelling, which is based on the results of stability testing storage conditions. All drugs

should be stored according to the conditions described on the label.

Temperature, relative humidity, and ventilation should be appropriate and should not adversely

affect the quality of pharmaceutical products during their manufacture and storage, or the accurate

functioning of equipment. The temperature acceptance limits that will be tested and verified

during the temperature distribution verification must be based on the label specification to prove

that the storage conditions reflects the labelling specifications. In case you have various storage

conditions, you need to test the smallest temperature range. The established acceptance limits will

inform us if there are excursions observed

during the mapping period. “All excursions

outside the labelled storage conditions must be

appropriately investigated and the disposition

of the stock in question must be evidence-

based (technical justification). Corrective

actions (CAPA) should be identified and

implemented following the investigation to

prevent reoccurrence”6.

5.1.5. Testing

The temperature distribution test is performed according to the procedure described in the

protocol, which identifies the steps required to perform and document the study. This test is

designed to allow analysis of temperature distribution inside the warehouse. It will be analyzed

as follows:

Warehouse temperature distribution verification - winter season

Warehouse temperature distribution verification - summer season

The temperature distribution during winter and summer seasons will be verified by conducting a

7-day to 14-day temperature mapping of the loaded warehouse by using a predetermined number

6 HPRA. Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medicinal Products and Active Substances, IA-G0011-1 Date 05/10/2011


© Cryopak 2015 14

of data loggers, which will be positioned as described in the protocol. Refer yourself to the section

5.1.2 Data Loggers Distribution for more details on where to install the data loggers.

The reading interval will be set at 15 minutes for the test. The temperature set point of all

thermostats will be documented. The external warehouse environmental conditions should be

taken into consideration. If these conditions are stable, a shorter length of time might be

appropriate. However, if the conditions are variable, more time might be required.

The temperature mapping should be repeated every 3-4 years. Mapping should also be redone

after any significant modification to the premises, stock layout, or heating system. Heat gain of

goods stored next to sun-facing windows, at high level in poorly insulated stores, or next to heaters,

should be considered.

The temperature distribution verification must be conducted by trained and experienced technical

personnel and must be documented in a scientific manner using an established format. This study

is meant to be representative and to be close to the real use of the warehouse. The temperature

distribution study is to be executed during normal working conditions.

5.2. Step 2 – Protocol Execution 5.2.1. Programming Data Loggers

Cryopak can provide customers with its iMiniUSB

pdf data loggers to perform the study. Using our

CFR 21 part 11 compliant software, ConsolePlus,

program each data logger according to the

parameters specified in the protocol.

To reduce the risk of human error to a minimum,

make sure to enter the data logger’s identification

number in the “Description” field (1). Once this is

done, physically label the data logger with the

same ID.

Select the temperature limits. These will only

make it easier to identify the temperature

excursion when doing the data compilation (2).

Once this is done, select the reading interval. This

parameter will determine how often the data

logger will take a measurement (3). Finally, hit the program button (4). Before disconnecting the

1

2

3

4


© Cryopak 2015 15

data logger, make sure all the lights blink on the data logger, meaning it was successfully

programmed.

5.2.2. Installing Data Loggers

Once you are ready to execute the temperature mapping, install the data loggers as per the

protocol’s plan. It is important to mention that the locations and heights indicated in the protocol

are approximate and might need to be adjusted. Make sure to document the exact location during

installation.

Secure the loggers in place to ensure they do not fall during the full study duration. They should

be attached to a stationary object such as shelving, racking, etc. Refer to the pictures below for more

details.

In the case of a large empty space, you can install data loggers on ropes hanging from the ceiling.

5.2.3. Documentation

It is crucial to properly document every section in the “Test Data Sheet” section of the protocol.

You must record any pertinent information and discussion of any unusual observations, exact data

loggers’ location, as well as any other information requested.

Every change to the protocol must be signed and dated.

5.2.4. Removing Data Loggers

Once the study is over, remove all the data loggers by using the warehouse plan provided in the

protocol. This will ensure no data logger is forgotten.

By simply connecting your data logger to a USB port, download all the data under .cvt, .csv and

.pdf formats. Send the files (or send the data loggers themselves) to the project engineer.


© Cryopak 2015 16

5.3. Step 3 – Report 5.3.1. Data Compilation

Once the study is over and the data loggers have

been removed, download the data and save all the

electronic files on your computer or network. All

logged data is secured in a file that cannot be

altered. Even if the original files usually require

proprietary software in order to open them, it is

often possible to save them in Adobe PDF format for

universal access and viewing. It is mandatory to

save the original and PDF files on a CD that will be

kept with the executed protocol for future audits. It is important to mention that the software used

to retrieve the data and generate reports must be compliant to PIC/S GMP Annex 11 and 21 CFR

Part 11 requirements7.

Data can also be exported into an Excel spreadsheet

for additional analysis. See Figures 5 and 6 for the

Excel cumulative data and graph of a 7-day

temperature mapping.

However, exporting the data to Excel does not

maintain the integrity of the data and is considered

transcription. For this reason, the original files must

be stored. To ensure that the data has not been

altered, a second person must verify all data

transcription and calculations performed in Excel.

5.3.2. Mean Kinetic Temperature (MKT)

Various regulatory authorities recommend using the MKT for establishing profiles of storage

facilities. They do not, however, reference the use of MKT for determining the environmental

effects (including light, humidity and temperature) during distribution.

The USP clearly states that determining the ability of pharmaceutical articles to maintain their

Pharmacopeia requirements of identity, strength, quality, and purity through distribution may

include, but is not limited to, the use of ICH stability studies, temperature cycling studies, stability

7PATTERSON, Brandon J. & Justin PAWLIK. Journal of GxP Compliance, Monitoring By Data Logging.

SECTION 1: DISPENSARY STORAGE AREA (ROOM# 119)

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Low Limit of 15°C

High Limit of 25°C

March 02, 2015February 23, 2015

Figure 5: Warehouse 7-day Temperature Graph

Figure 6: Warehouse 7-day Temperature Cumulative


© Cryopak 2015 17

shipping studies, ongoing regulatory stability commitment studies, market experience portfolios

and product labelling commitments.

Nevertheless, a small number of manufacturers, distributers and shippers of temperature sensitive

pharmaceuticals rely solely on MKT calculations to justify their shipping methods and packaging

requirements, thereby sending their products out in unqualified - and possibly inadequate -

packaging, incapable of maintaining recommended storage requirements, and potentially putting

their product at risk. If needed, the MKT is a calculated fixed temperature that simulates the effects

of temperature variations over a period of time. It expresses the cumulative thermal stress

experienced by a product at varying temperatures during storage and distribution.

5.3.3. Calibration and Post-Calibration Requirements

Calibration is a common topic in any pharmaceutical activity that involves

instruments and data logging is no exception. When data are being

collected for a mapping study, the instruments must be calibrated using

an appropriate tolerance and range for the measurements taken. The

calibration should be National Institute of Standards and Technology

(NIST) traceable and be documented in a manner consistent with Good

Documentation Practices (GDPs).

They should also be post-calibrated after the study to ensure the

instrument is still operating (in a calibrated state during the study period)

within its original specifications by comparing the compensation curves

of the previous calibration and the new calibration results obtained to

prove the accuracy is within the specification. The Health Product

Regulatory Authority (HPRA) have recently acknowledged that a 10%

minimum of the data loggers should be post calibrated following this

type of thermal mapping exercise. Only single-use devices that are

supplied with a manufacturer’s calibration certificate do not need to be

re-calibrated.

5.3.4. Data Analysis

The Excel exported data and graphs become part of a complete report that identifies any

undesirable temperature patterns and recommends potential solutions.

The report contains copies of all data logger calibration certificates, questionnaires, and other

information used to complete the study. If the mapping study indicates undesirable conditions,


© Cryopak 2015 18

facility owners can take a wide range of measures, depending on the problems’ severity. They

include:

Removing products from problem areas (such as hot spots near ceilings);

Changing work practices (such as keeping doors open or closed);

Changing racking or shelving configurations;

Repositioning racks or shelving to improve air circulation;

Changing the location of heating devices;

Installing an air conditioning system;

Improving ventilation;

Installing more or larger-capacity fans;

Adding humidification or dehumidification;

Installing an HVAC control system.

The analysis can also identify the storage area’s hot and cold spots. The purpose of determining

hot and cold spots is to identify the locations where the environmental monitoring system (EMS)

sensors should be installed to record the most vulnerable spots in the storage area and avoid any

temperature excursions that could affect the products. Hot and cold spots need to be determined

seasonally.

Determining hot spots: Any zone of the warehouse where the highest average temperature

was recorded closest to the upper limit.

Determining cold spots: Any zone of the warehouse where the lowest average temperature

was recorded closest to the lower limit.

An attractive option is to install monitoring sensors that communicate continuously with a Part 11

compliant environmental monitoring system (EMS). The EMS can be programmed with alarm set

points to alert service technicians by e-mail, pager or telephone to notify changes in space

conditions before it has any effect on the products.

Real-time monitoring provides an added assurance that space conditions match product storage

specifications. A continuous record can also be valuable in case of regulatory authorities’ inquiry

or audits - all records must be retained for a duration as in accordance with the legal requirements

and be readily retrievable – especially if the monitoring information is combined with the detailed

inventory data pharmaceutical companies already keep. With both kinds of data in hand, a


© Cryopak 2015 19

company could document the location in which a given pharmaceutical product was stored and

the temperature conditions that existed while it was there.

6. CONCLUSION

Temperature mapping is a valuable exercise. If regulatory requirements clearly explain when a

mapping study has to be done, internal procedures should detail how often this exercise has to be

repeated over the years. Initially, when a Drug Establishment License has to be submitted, all

protocols must be ready for your auditors. Extreme season mappings are in most cases executed

winter and summer. However, in some parts of the world, humidity and other factors should be

taken into consideration.

Even if a company Quality Department is well equipped to perform a mapping project, partnering

with an external company can bring an independent approach. A clear assessment of the client’s

needs, as well as a good knowledge of national and international regulatory are crucial. This first

step will help with the protocol writing. The protocol must be complete and detailed, and clear

about the approach to be taken and how the study will be performed.

Determining the position of loggers within your area to be mapped is essential: it is always better

to have more loggers than less and a scientific rational is always appreciated by all auditors and

quality departments. Different 3D models exist, and the protocol has to explain the rational of

logger placement.

Clients will have to make sure that loggers used with their appropriate software are compliant for

their industry for calibration and also to make sure that it complies with other regulatory

requirements such as CFR Part 11, NIST traceability and validation (Installation, Operational, and

Performance).

Final report conclusions must be clear and identify the pass and fail outcomes of the study. If no

acceptance criteria have been written in the protocol, it will be the customer’s responsibility to take

appropriate actions according to the results obtained.

We strongly recommend that mapping studies be repeated on a regular basis -every 3 or 4 years

to demonstrate to your auditors that you are in control of your cold chain, and that products you

are responsible for are maintained within a proper temperature range.


© Cryopak 2015 20

7. REFERENCES

PARENTERAL DRUG ASSOCIATION. Technical Report No.64 – Active Temperature Controlled

Systems: Qualification Guidance, PDA, 2013, 58p.

(2013/C 68/01) Good Distribution Practice of Medicinal Products for Human Use

ROBEY, Sarah. Our blog Whichwarehouse, [http://www.whichwarehouse.com/blog/news/tips-

pharma-storage-speciality-warehouse-storage-warehouse-space/] (page consulted on April 14th,

2015)

USP General Chapter <1079> Good Storage and Shipping Practices, USP 28, Suppl. 2, August 1st,

2015.

WILLIAMSON, Mike. Mike Williamson Validation Blog, [www.mikewilliamsonvalidation.wordpress.com/2013/01/02/qualifying-controlled-warehouse-space/] (page consulted on April 14th, 2015) HPRA. Guide to Control and Monitoring of Storage and Transportation Temperature Conditions

for Medicinal Products and Active Substances, IA-G0011-1 Date 05/10/2011

PATTERSON, Brandon J. & Justin PAWLIK. Journal of GxP Compliance, Monitoring By Data

Logging.

Documents

Warehouse Mapping Process Best Practices for Warehouse es ... · ISPE Good Practice Guide – Cold Chain Management (2011). Irish Medicines Board Guide to Control and Monitoring of