Approach for performance qualification of cold rooms and chambers

Cold storage is a relatively simple cold room that is commonly used to store material between 2[degrees] to 8[degrees]C. Such cold rooms are now available commercially as walk-in chambers and are used for the storage of critical pharmaceutical products, samples, and raw materials where excursions in temperature conditions may affect the quality of stored material(s) in terms of their appearance (color), consistency, potency, and impurity levels. Hence it is essential to qualify cold storage chambers under the worst-case scenarios.

Some pharmaceutical manufacturers perform only Installation Qualification (IQ) and Operational Qualification (OQ) of cold rooms, but the Performance Qualification (PQ) is also essential because data-based conclusions should be arrived at by challenging the system for all the attributes that may have bearing on the performance of the chamber for maintaining the desired temperature conditions.

OFFICIAL AND STANDARD REFERENCES

USA

21CFR 211.142 and 211.150: Storage and Distribution

USP Chapter 1079: Good Storage and Shipping Practices

"Qualification of cold equipment or stores"--On a regular basis, qualification procedures should be independently conducted on equipment in cold stores to guarantee their suitability and proper functioning. The procedure should demonstrate the temperature profile for both air and product temperatures when chambers are empty as well as when loaded. The procedure should also demonstrate the time taken for temperatures to exceed the maximum temperature in the event of a power failure. Qualification should consider thermal fluctuations that occur during stock replenishment and order removal. The results of the qualification should demonstrate the ability of the equipment to maintain the required temperature range in all areas, defining any zones which should not be used for storage such as those areas in close proximity to cooling coils, doors, or cold air streams from equipment ventilation. The variability of the system can be characterized by using the relative standard deviation. Thermal monitoring should establish that the system is rugged in that its temperature profile is consistent and reliable.

Medicines and Healthcare Products Regulatory Agency (MHRA)

Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2007, Section IV "Guidance on Wholesale Distribution Practice" pg 358:

"Large commercial refrigerators and walk-in cold rooms should be monitored with an electronic temperature--recording device that measures load temperature in one or more locations, depending on the size of the unit.... Internal air temperature distribution should be mapped on installation in the empty and full state, and annually thereafter, under conditions of normal use."

Irish Republic

Irish Medicines Board: Guide to Control and Monitoring of Storage and Transportation Temperature Conditions for Medicinal Products and Active Substances PDA Technical Report No. 39

Cold chain guidance for medicinal products: maintaining the quality of temperature-sensitive products through the transportation environment.

World Health Organization

Guidelines on Good Distribution Practices (GDPs) are incorporated into volume 2, good manufacturing practices and inspections, in "Quality Assurance of Pharmaceuticals."

Canada

Food and Drug Regulations, Section C.02.015 Guidelines for Temperature Control of Drug Products during Storage and Transportation (Guide--0069)

* Storage is a critical parameter in maintaining the quality, safety, and efficacy of a medical product.

* Storage condition is an important parameter to maintaining the stability of the product.

* Product must be stored in accordance with the requirements of its marketing authorization.

QUALIFICATION PARAMETERS

Normally, the Design Qualification (DQ), Installation Qualification (IQ), and Operational Qualifications (OQ) of the cold room are performed prior to the Performance Qualification (PQ). The IQ/OQ of the chamber are easy to perform and document, and a majority of pharmaceutical manufacturers comply with this requirement. The supplier of the equipment also helps in performing these qualification tests for IQ and OQ.

Now the question arises as to why and how the performance of the cold storerooms or chambers should be qualified.

The purpose of the PQ of the cold room is to establish sufficient data to ensure that the cold room is capable of:

* Maintaining the desired temperature range throughout the cold room under extremes of external temperature.

* Identifying potential hot spot(s) or cold spot(s) in the chamber.

* Determining the time required for conditions to return to specified parameters (as desired) in case of excursions.

* Determining the effects of electrical or refrigeration source fluctuations or power failure--especially where back-up units are employed.

While designing the validation study (protocol), understanding the design of the cold room is helpful. A cold room or chamber is a room in the shape of a cubical, made with prefabricated Polyurethane Foam (PUF) insulated panels or of brick and mortar with insulation to maintain the desired conditions of temperature and humidity within. Knowing that the seal between any two panels is integral, and that there are no openings, other than the door, which may disturb the conditions of the chamber. Understanding of the design of the chamber is needed to decide on the number of probes and their locations for temperature monitoring.

Parameters that may affect the Condition of the Cold Room

It is desired that the cold room chamber provide controlled temperature conditions. There are several parameters that may have an impact on the condition of the cold room. These include:

* External temperature conditions

* Door opening time during handling of material in and/or out of the Cold Room

* Power breakdown

* Air flow velocity through fans (not less than 2400 CFM (cubic feet per minute))

* Too much material stored in the room (thermal load)

Therefore, during the PQ study the above listed parameters should be subjected as simulated worst-case conditions because these parameters may have an impact on the performance of the cold room.

TEMPERATURE MAPPING

The temperature mapping is accomplished by using temperature indicating probes coupled with a data logger for data accusation. Questions may be asked regarding the number of probes to be utilized and their placement in the cold room for temperature mapping in the empty room and the loaded room. The basic consideration should be that the probes are distributed uniformly in the room and should cover all the vertical planes. A minimum of fifteen (15) probes were considered adequate for mapping of the temperature of the cold room to verify its performance (1).

Justification for Probe Locations

Probe location should be decided logically, strategically, and scientifically. The following locations cover the entire room:

Probe No 1:

External environment outside the cold room

Probe No 2:

To calibrate along with the in-built temperature and humidity probe of the room

Probe No 3:

Near to the door opening

Probe No 4:

At the centre of the room

Probes No 5, 6, 7, 8:

Top layer four corners of the room, but not at the extreme corners

Probes No 9, 10, 11, 12:

Bottom layer four corners of the room, but not at the extreme corners

Probe No 13:

In mid-region between the door and Probe No 4

Probe No 14:

In mid-region between back of wall and Probe No 4

Probe No 15:

In mid-region between floor and Probe No 4

By placing the probes in these positions, you will completely cover the room and all the planes of the cuboid (chamber). Such mapping is also conducted as an operational qualification to check whether the components or utilities are capable of providing the desired conditions.

PERFORMANCE QUALIFICATION STUDIES

For performance qualification, two separate studies are required to be performed. One study should be completed for the temperature distribution in an empty room or chamber running continually for 24 hours. The second would be a temperature distribution study in a loaded room or chamber. Load the boxes with material that simulates a thermal load, such as starch, lactose, or water in bottles (in case liquid is to be stored in the chamber) record the temperature intermittently for 75 hours each, for three seasons (i.e., peak Summer, Monsoon (as applicable), and Winter) to demonstrate that there is no effect of seasonal variations on the temperature controls in the cold room.

STUDY METHODOLOGY

For Blower Performance

The CFM of the blower should be checked and recorded at each prequalification (PQ) test point. This information shall help to decide whether the air circulation from the blower is the cause, if the condition is not achieved at one or more locations, or it is the cause of the loading pattern of the materials in the chamber, where the temperature is being monitored.

[FIGURE 1 OMITTED]

For Empty Room or Chamber

Set the temperature of the cold room at the desired temperature and operate the cold room according to Standard Operating Procedure (SOP). Perform temperature mapping for 24 hours with five minute sampling intervals. After completion of the study, review the data to identify the hot spot and cold spot areas in the cold room.

For Loaded Room or Chamber

Load the entire room with dummy boxes (as described earlier under "PERFORMANCE QUALIFICATION STUDIES") on the pallets or racks up to its 80% capacity, maintaining gaps between boxes for uniform circulation of air. Set the temperature of the cold room at the desired temperature and operate the cold room according to SOP. Perform the temperature mapping for 72 hours with five minute recording intervals. After completion of the study, review the data and identify the hot spots and cold spots in the loaded cold room.

SIMULATIONS

The following worst-case conditions should be simulated:

For Power Failure Condition

A power failure study should be conducted at a peak temperature hour in summer. When the cold room is in operation and within the set temperature level, switch the power off from the mains. Record the temperature at intervals of one minute for simulation of conditions of power outage.

Continue recording the temperature until the temperature within the chamber falls outside the acceptance criteria. When the temperature is out of limit at the hot spot area identified earlier in the study, switch ON the mains and continue recording at intervals of one minute until the desired temperature is achieved. Record the time required for conditions to go beyond the limits from normal under the simulated situation of power failure, and again, the time required for regaining the desired conditions upon power resumption.

For Open Door Condition

The open door condition study should be conducted at a peak temperature hour in summer. When the cold room is in operating condition and the temperature is within the set value, open the door and record the temperature at intervals of one minute. With door open, continue recording the temperature until the temperature within the cold room is out of acceptance criteria.

When the temperature is out of limit at the hot spot identified earlier in the study, close the door and continue recording until the desired conditions are regained. Record the time required for conditions to go beyond the limits, from normal under the simulated situation of the door being opened and the time required to regain the desired conditions upon closure of the chamber's door.

RE-QUALIFICATION

Performance Qualification of cold room to be requalified for:

* Replacement of existing room component with a new one, which can have a direct impact on the performance of the cold room.

* Any major modification in a key machine (such as the compressor) which can affect the performance of the cold room.

The PQ should be conducted annually under normal usage.

CONCLUSION

The temperature for the cold room or chamber is the critical parameter, since excursions in temperature conditions may affect the quality of stored material(s). It is essential, therefore, to qualify cold room performance under worst-case scenarios. The approach described above for conducting the performance qualification of such cold rooms or chambers, with the consideration of all possible challenges that may have a bearing on the desired acceptance criteria addresses each potential issue. Conducting the studies following the methodology outlined, the impact of situations such as opening the door, or power failure for a given period can be known. Further, through these procedures, it is possible to identify the hot spot and cold spot and the time required to regain the desired temperature conditions if disturbed because of adverse conditions.

REFERENCES

1. Michael J.A., Anderson N.R., "Sterilization Validation." In R.A.Nash, A.H.Wachter, eds., Pharmaceutical Process Validation 3rd Ed. New York: Marcel Dekker, PP. 100(2003).

2. Food and Drug Administration, 21CFR 211.142 and 211.150 (Storage and Distribution).

3. The United States Pharmacopeia, Chapter 1079: Good Storage and Shipping Practices.

4. Medicines and Healthcare Products Regulatory Agency, Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2007, Section IV "Guidance on Wholesale Distribution Practice" pg 358.

ABOUT THE AUTHORS

Francis Fernandes is Quality Assurance Manager of Glenmark Pharmaceuticals Ltd, Colvale, Goa, India. He has over eight years in the pharmaceutical industry in areas that include manufacturing, technical services, and Quality Assurance. Mr. Francis Fernandes specializes in the validation of equipment, utilities, manufacturing, cleaning, and product processes. He can be reached by e-mail at fransha.ape@gmail.com, francisf@glenmarkpharma.com

Dr. Subhash Pande is Vice President Corporate Quality Assurance, in Glenmark Pharmaceutical Limited, Mumbai. Having over 20 years of experience in manufacturing, Quality Assurance of APIs, Sterile, Oral, and Semi-solid Oral dosage forms, Teaching and Research. A life member of Indian Pharmaceutical Congress and ISPE, he has more than twelve research papers published in National and International journals. He is also associated with IBC Asia, for training. He also is involved in academic activities in the capacity of Guest Lecturer and as Examiner. He can be reached by email at subhashp@glenmarkpharma.com or subhashp@gmail.com.

Article Acronym Listing

1.2   Objectives 

The objective is to provide guidance on how to carry out the three types of qualification
needed to meet the requirements of Good Storage Practice in temperaturecontrolled
areas.  These are Installation
Qualification (IQ); Operational Qualification (OQ), and
Performance Qualification (PQ). 

1.3   Target readership 

This document is relevant to wholesalers, warehouse
operators, distributors, dispatchers and 3PLs who store TTSPPs. The specific
target audience within these organizations 

includes
those who have direct responsibility for quality management, for example, 

Quality
Assurance (QA) Managers and Operations Managers. 

2. Guidance 

The purpose of qualification in the pharmaceutical and
medical sector is to ensure that equipment or ancillary systems are properly
installed, work correctly, and produce the specified performance outcomes under
routine operating conditions. 

2.1   Associated materials and equipment 

A qualification operation requires a sufficient number
of electronic data logging monitors (EDLMs) to ensure that qualification activities
can be carried out correctly. In addition, suitable computer equipment and software is
needed to store and analyse the data. The chosen EDLMs should have the
following characteristics: 

•           Be
technically suitable for the specific task and the intended operating

environment;

•           Provide
a reliable and continuous reliable record of time-temperature data;

•           Have
an appropriate temperature range so that all anticipated temperature

extremes can be recorded (e.g. from -30°C to +60°C). 

•           Have a user-programmable data sampling
period with time intervals ranging from 

one minute to 15 minutes or more; 

•           Have a NIST- traceable 3-point calibration
certificate and have a guaranteed error 

of no more than ± 0.5°C at each calibration point. 

•           Recorded time-temperature data should be
downloadable to a computer system 

for subsequent analysis; 

•           Data storage and analytical software should
comply with applicable regulatory 

requirements (e.g. FDA 21 CFR part 11). 

2.2   Introduction to qualification 

Qualification is part of validation, but the individual
qualification steps do not in 

themselves constitute process validation. Validation is
the entire process by which a 

product is obtained from a manufacturer or distributor
and is examined and tested before it is formally approved for routine use. 

A qualification exercise generally consists of three
sequential phases: Installation 

Qualification (IQ), Operational Qualification (OQ), and
Performance Qualification (PQ). 

a.   Installation
Qualification: The purpose of installation qualification (IQ) is to ensure 

            that a new piece of equipment
- together with all its related systems or sub-

systems - has been installed in accordance with the
relevant installation drawings and specifications. 

b.   Operational
Qualification: A successful operational qualification (OQ) exercise 

provides assurance that equipment which has successfully
passed the IQ stage 

operates in an effective and consistent manner. As a
general rule, OQ is carried out on equipment when it is empty. 

c.   Performance
Qualification: Following OQ, a performance qualification (PQ) 

provides additional assurance through further testing
that the equipment will 

work correctly in the intended operational setting. The
outcome of a successful PQ 

exercise is a formal confirmation that the
equipment, associated systems and operational processes can be ‘released’ for
routine use.  In contrast to OQ, PQ is
carried out on equipment when it is full. 

2.2.1   Qualification
applied to temperature-controlled storage 

Qualification is commonly used to validate pharmaceutical
manufacturing processes but it can also be applied to the pharmaceutical
supply chain in general, and to temperaturecontrolled storage processes and
equipment in particular. 

In this later context, temperature-controlled storage
covers any area where TTSPPs have 

to be stored within a controlled temperature range (e.g.: 2-8°C, 15-25°C).  This includes: 

•  
Active temperature-controlled storage equipment, including ultra-low
freezers, 

            freezers, freezer rooms,
refrigerators, cold rooms and controlled-ambient stores. 

•  
Actively temperature-controlled transport equipment. This includes
refrigerated 

            and
temperature-controlled trucks and vans, refrigerated and temperature-

controlled ocean containers.  Refer to the companion Technical Supplement:
Qualification of temperature-controlled road vehicles. 

•  
Passive temperature-controlled packaging systems (shipping containers).
This 

            includes insulated containers
used to maintain product temperature during road 

and air transport. Refer to the companion Technical
Supplement: Qualification of shipping containers. 

All temperature-controlled equipment and systems used to
handle, store and distribute TTSPPs should be qualified. 

An integrated IQ, OQ and PQ procedure is commonly used to
qualify temperature-

controlled storage areas. Ideally the IQ, OQ and PQ
procedures should be applied in a 

progressive
and coordinated way, from the installation up to the final performance 

verification.
However this may be more difficult if the storage areas and equipment are 

already
in use. 




2.2.2   Installation
qualification 

The IQ process should be completed first. Its purpose is
to ensure that the storage area 

and all its associated equipment and systems are clearly
identified and have been correctly 

installed.
This step must be completed before any further functional or operational tests 

are carried out. 

Specifically, an IQ process should: 

a.   Identify the
storage area and the equipment and systems required for it to operate 

            correctly. Establish that
all systems operate as specified; 

b.   Establish the
calibration status of all measuring devices (e.g. controllers and 

            sensors); 

c.   Ensure that
standard operating procedures (SOPs) or work instructions are up-to-

            date and fit for purpose;


d.   Ensure that
an effective preventive maintenance programme is in place.

2.2.3  
Operational and performance qualification 

Once the IQ stage has been completed,
the OQ and PQ can generally be carried out 

together as a single sequence of inspections and tests.
These inspections and tests should be chosen to suit the specific
characteristics, performance needs and operational 

conditions of the storage area being qualified. 

Operational qualification is carried out with the
storage area empty. It typically involves the following activities: 

•  
Control panel tests and checks; 

•  
Alarm system tests and checks; 

•  
Assessment of temperature control and temperature distribution in the
empty 

            storage space or equipment8; 

•  
Power failure tests and checks. 

Performance qualification is carried out with the storage
area fully operational, loaded and 

allowed to reach stabilized conditions. The following tests and checks should
be carried 

out: 

•   Temperature control and temperature
distribution. 

•  
Temperature recovery following a door opening. 

2.3   Qualification protocols 

Prepare, review and approve a detailed and comprehensive
protocol before the qualification process begins. 

The qualification protocol should be a comprehensive
document, which guides the user 

through
the IQ, OQ and PQ processes and helps ensure that all temperature-controlled 

storage
areas are correctly qualified. Each of the three protocols can be more or less 

generic. However generic documents should never be used unthinkingly; they
should 

always be adapted to the specific type of temperature-controlled storage area;
each 

installation must be linked to and qualified against its own specific
qualification protocol. 

The qualification protocol should include the following
sections: 

a.   Approval page
and change control history. 

b.   Acronyms and
glossary. 

c.   Description
and rationale. 

d.   Scope and
objectives. 

e.   Key
parameters. 

f.          Procedures.

g.   Qualification
report template. 




2.3.1   Approval page and
change control history 

Include a standard template for recording approvals and
changes to the document. The following is an example











 


  

  

Approvals

  

  

Name

  

  

Date

  

  

Signature

 

  

  

Authorized by:

  

  




  

  




  

  




 

  

  

Reviewed by:

  

  




  

  




  

  




 

  

  

Revised by:

  

  




  

  




  

  




 

  

  

Original author:

  

  




  

  




  

  




 





Version history 




 


  

  

No

  

  

Date

  

  

Description of change

  

  

Reason for change

 

  

  

1

  

  




  

  

Original

  

  




 

  

  

2

  

  




  

  




  

  




 

  

  

3

  

  




  

  




  

  




 

  

  

4

  

  




  

  




  

  




 

  

  

5

  

  




  

  




  

  




 


If the protocol has been prepared by a qualified
third-party, it should be authorized by the responsible person within the commissioning
organization. 




2.3.2   Acronyms and
glossary 

Define the acronyms and technical terms used in the
protocol. 




2.3.3   Description and
rationale 

Describe the installation to be qualified and the
equipment and related systems to be 

included in the qualification exercise and outline the
reasons for carrying out the exercise. 




2.3.4   Scope and
objectives 

Clearly define the scope and objectives of the
qualification exercise. 




2.3.5   Key parameters 

Describe the key parameters for the operation of the
installation. 




2.3.6  
Procedures 

The protocol for a specific installation should describe
every relevant test or check procedure in detail, as follows: 

a.   Title: Briefly
describe the test or check; 

b.   Target: Name
the target system, sub-system or component; 

c.   Procedure:
Clearly describe the test or check procedure as a step-by-step process. 

            Specify any associated
materials or test equipment required; 

d.   Acceptance:
Define the acceptance criteria; 

e.   Data
collection: Include templates for all required data collection and test sheets.


A
generic set of IQ, OQ and PQ tests and checks is outlined in sections 2.4 to
2.7 below. 








2.3.7  
Qualification report template 

The protocol should contain a template for the
qualification report. This should include 

everything
needed to satisfy internal compliance rules and regulatory requirements, as 

follows: 

a.              Introduction:
Describe the objectives of the qualification exercise. 

b.              Summary:
Outline the results of the qualification exercise. Include a summary of all 

recorded deviations. 

c.          Conclusions
and recommendations: State whether the installation can be used for 

routine operations. List all key recommendations that
need to be acted upon; this 

should
include a complete list of all changes that need to be made to the 

installation
to correct reported failures recorded on the qualification inspection 

and
test data sheets. 

d.             Report
annexes: Append the following supporting material: 

−    Raw data as
recorded on the appropriate inspection and test data sheets (see 

            below). In addition, include
all associated spreadsheets and graphs. 

−    Key documents
and notes prepared during the qualification exercise, together 

            with any other supporting
material. 

−    Deviation
reports, including Corrective and Preventive Actions (CAPA) forms, if 

            required. 

−    Calibration
certificates for all EDLMs used. 

−    Calibration
certificates for the control and monitoring systems that form part 

            of the installation. 

−    List all
members of the qualification team, and their designations. 

All data sheets, results, spreadsheets and graphs must be
reviewed by an independent person who was not involved in conducting the
qualification exercise. The reviewer should confirm, approve and sign results of
the major tests and checks. 




2.3.8   Approval process 

If qualification is carried out as an in-house process,
the IQ/OQ/PQ protocols and 

subsequent qualification reports must be authorized by
the responsible manager(s) and quality assurance personnel within the
organization. 

If qualification is carried out by a qualified
third-party, both the IQ/OQ/PQ protocols and subsequent qualification reports
must be approved by the responsible person in the thirdparty organization. 

2.4   Installation qualification 

The purpose of installation qualification is to establish
that all elements of the storage area, including building work, equipment,
systems, sub-systems and components are in accordance with the installation drawings and
specifications. The first stage is to itemise all these key elements.
The next stage is to establish how each element should be 

inspected
and tested in order to confirm compliance. 

Once these preliminary stages have been completed,
on-site inspection and testing can begin. Proceed as follows: 








•           Carry
out a detailed inspection of the storage area and all associated building 

works. 

•           Carry
out a detailed inspection of the electrical services.

•           Carry
out a detailed inspection of the mechanical services.

•           Carry
out tests to confirm that the specified environmental condition requirements

have been met.

•           Identify,
list and inspect the spare parts 
supplied as part of the installation.

•           Identify,
list and inspect any auxiliary equipment associated with, but not part of

the installation, such as standby generators, security
systems and the like. 

•           Confirm that satisfactory arrangements are
in place to ensure an effective 

preventive maintenance programme for the complete
installaton. 




2.4.1    Identifying
critical components 

Although all parts of a temperature-controlled
installation should be included in the IQ, there are certain critical elements
that merit particularly close attention. 

Refrigerators, freezers and other simple equipment: The
critical parts of this type of 

equipment are the thermostat and its associated control
sensor and the temperature monitoring device (thermometer or recorder) and its
sensor; this may be a separate component such as a disposable 30 day
temperature recorder9. 

Complex equipment: This includes freezer rooms, cold
rooms, pick coolers and more 

complex and specialized refrigerators and freezers, with
a longer list of key components. Critical parts include the controller, sensor,
cooling unit, condenser and evaporator. 
For freezer rooms and cold rooms, the room enclosure itself
is also critical because these are site assembled from separate panel elements10.
All of these key components should be identified, listed, described and
checked. 

If the equipment has duplicate or multiple instances of
any components or systems, each 

one should be checked. Critical components and systems that are directly
involved in 

temperature control and measurement should also be checked for accuracy and 

calibration. Calibration certificates should be checked and copies included in
the IQ report. 




2.4.2  
Checking installed systems, sub-systems and components 

Table 1 shows the type of record used to check and record
installed systems and components. The example given here is for a cold room
refrigeration unit. 

Table 1 - Example of an
IQ inspection and test table 




 


  

  

Sub-system or component inspection and test table

 

  

  

Location:

  

  

SOUTH WAREHOUSE

 

  

  

System:

  

  

Cold room #1

 

  

  

Sub-system/component:

  

  

Refrigeration unit #1

 

  

  

Inspection or test:

  

  

Inspection:

  

  

Test:

 

  

  

Type of inspection/test:

  

  

IQ protocol: visual check RFU-01

 

  

  

Details:

  

  

Specified

  

  

As
  found

  

  

Pass or Fail

 

  

  

Manufacturer:

  

  

ABC refrigeration

  

  

ABC refrigeration

  

  

Pass

 

  

  

Model:

  

  

TTW50

  

  

TTW40

  

  

Fail

 

  

  

Serial number:

  

  

Not specified

  

  

TTW40-1310-025

  

  

Fail

 

  

  

Internal ID number:

  

  

CR1/RFU01

  

  

CR1/RFU01

  

  

Pass

 

  

  

Deviation report ref:

Enter ‘none’ if no deviation

  

  

DEV/001

 

  

  

Inspected by:

  

  

AG

  

  

Date:

  

  

27 Oct 2013

 

  

  

Checked by:

  

  

JB

  

  

Date:

  

  

5 Nov 2013

 


  

  

  

  

  

 



For each system, sub-system or component, the table
allows the IQ inspector to list the 

critical attributes of what was originally specified in
the requirements specification or on the installation drawings (the ‘specified’
column), what was actually installed (the ‘as found column) and whether or not
it complies (the ‘pass or fail’ column). 

a.              Specified
conditions: The ‘location’, ‘system’, component’ cells and the ‘specified’ 

column should be completed before the inspection begins.
The same applies to the 

subsequent
Tables 2 to 4. Pre-filling the table helps the IQ inspector to locate the 

listed item and check that it has been installed correctly. Where details are
not 

available - in the above example the serial number of
the refrigeration unit - enter 

‘not specified’.  In addition, record
whether an inspection and/or test(s) are to be 

carried
out to assess compliance and describe the type of inspection and/or test(s) 

to be used. Key this back to the relevant section of the
qualification protocol. 

b.              As
found column: Use this column to record details of the item as found at the
time 

of the inspection. 
To achieve a ‘pass’, the installed sub-system or component must meet
or exceed the specified condition. In the Table 1 example, although the 

refrigeration
unit has been supplied by the specified manufacturer, the unit 

installed has a lower power rating than the one specified. 

c.          Pass
or Fail column:  Compliance is achieved
when an item fully meets or exceeds 

the specification or the specified performance
conditions. In the Table 1 example, the correct manufacturer has supplied the
unit, so this is a ‘pass’. However, the refrigeration capacity of the installed
unit is too small, so this is a ‘fail’

.   Deviation
report: Wherever a deviation is observed, this must be recorded on a 

            separate deviation report
form. Each inspection table should include a space to 

record a cross-reference to the relevant deviation
report. If there are no 

deviations, enter ‘none’ - see example of deviation report in Annex 1). 

e.  
Signatures:  The completed sheet
should be signed or initialled by the inspector 

            and checked by the designated
reviewer. 

Use drawings, photographs and other supporting material
to amplify and support the information recorded in the table. 




2.4.3   Checking
electrical systems and requirements 

Because the installed electrical system typically
connects to multiple components, it 

requires a separate inspection and qualification
procedure. Table 2 can be used to record the overall compliance of the installed
electrical system. Table 3 is used to identify and check
the critical components of the system. 

Table 2 - Overall compliance check for electrical
installation 




 


  

  

Electrical
  installation: system compliance check 
  sheet

 

  

  

Location:

  

  

SOUTH WAREHOUSE

 

  

  

System:

  

  

Electrical installation

 

  

  

Sub-system/component:

  

  

3-phase supply to cold room #1

 

  

  

Inspection or test:

  

  

Inspection:

  

  

Test

 

  

  

Type of inspection/test:

  

  

IQ protocol: visual check ELEC-01

 

  

  

Items

  

  

Specified

  

  

As
  found

  

  

Pass or Fail

 

  

  

Main voltage (V):

  

  

415 V

  

  

415 V

  

  

Pass

 

  

  

Cycles (Hz):

  

  

50Hz

  

  

50Hz

  

  

Pass

 

  

  

Amperage (A):

  

  

100 A

  

  

100 A

  

  

Pass

 

  

  

Phase:

  

  

3

  

  

3

  

  

Pass

 

  

  

Inspected by:

  

  

AG

  

  

Date:

  

  

27 Oct 2013

 

  

  

Checked by:

  

  

JB

  

  

Date:

  

  

5 Nov 2013

 


  

  

  

  

  

 



Table 3 - Electrical installation: critical
component checks 




 


  

  

Electrical installation: critical component check sheet

 

  

  

Location:

  

  

SOUTH WAREHOUSE

 

  

  

System:

  

  

Electrical installation

 

  

  

Sub-system/component:

  

  

3-phase supply to refrigeration unit A

 

  

  

Inspection or test:

  

  

Inspection

  

  

Test:

 

  

  

Type of inspection/test:

  

  

IQ protocol: visual check ELEC-05

 

  

  

Electric supply

  

  

Specified

  

  

As
  found

  

  

Pass or Fail

 

  

  

Breaker location / service

panel

  

  

Panel A

  

  

Panel A

  

  

Pass

 

  

  

Circuit / breaker number

  

  

Not specified

  

  

RFU-1

  

  

Pass

 

  

  

Circuit voltage (V)

  

  

315

  

  

315

  

  

Pass

 

  

  

Circuit amperage (A)

  

  

30 A

  

  

20 A

  

  

Fail

 

  

  

Circuit phase

  

  

3

  

  

3

  

  

Pass

 

  

  

Emergency power?

  

  

Required

  

  

Yes

  

  

No ☐

  

  

Pass

 

  

  

Isolating switch?

  

  

Required

  

  

Yes

  

  

No ☐

  

  

Pass

 

  

  

Is the electrical supply

compatible with electrical

requirement?

  

  




Required

  

  




Yes

  

  




No

  

  




Fail

 

  

  

Grounded?

  

  

Required

  

  

Yes

  

  

No

  

  

Pass

 

  

  

Special isolation /

shielding?

  

  

Not required

  

  

Yes

  

  

No

  

  

Pass

 

  

  

Is the circuit breaker

properly identified?

  

  

Required

  

  

Yes

  

  

No

  

  

Pass

 

  

  

Inspected by:

  

  

AG

  

  

Date:

  

  

27 Oct 2013

 

  

  

Checked by:

  

  

JB

  

  

Date:

  

  

5 Nov 2013

 


  

  

  

  

  

  

 



The service panel and circuit breakers that apply to the
various critical components 

should
be clearly labelled both at the service panel itself and at the component. 

Table 4 - Environmental condition, control and
monitoring checks 




 


  

  

Environmental control and monitoring system check sheet

 

  

  

Location:

  

  

SOUTH WAREHOUSE

 

  

  

System:

  

  

Cold room #1

 

  

  

Sub-system/component:

  

  

As above

 

  

  

Inspection or test:

  

  

Inspection:

  

  

Test:

 

  

  

Type of inspection/test:

  

  

IQ protocol: visual check ENV-01 and instrumented

measurement ENV-02

 

  

  

Items

  

  

Specified

  

  

As
  found

  

  

Pass or Fail

 

  

  

Cleanliness:

  

  

All surfaces clean

  

  

Floor dusty

  

  

Fail

 

  

  

Fumes:

  

  

None perceptible

  

  

None perceptible

  

  

Pass

 

  

  

Vibrations:

  

  

None perceptible

  

  

RFU #1 vibrating

  

  

Fail

 

  

  

Temperature control:

  

  

Single sensor

  

  

Single sensor

  

  

Pass

 

  

  

Humidity
  control:

  

  

No active control

  

  

No active control

  

  

Pass

 

  

  

Temperature monitoring:

  

  

3 sensors

  

  

3 sensors

  

  

Pass

 

  

  

Humidity
  monitoring:

  

  

None

  

  

None

  

  

Pass

 

  

  




Temperature (°C):

  

  




+2°C to +8°C

  

  

+5.5°C (sensor 1)

+6.1°C (sensor 2)

+4.9°C (sensor 3)

  

  




Pass

 

  

  

Humidity (% RH):

  

  

60% to 75%

  

  

70%

  

  

Pass

 

  

  

Inspected by:

  

  

AG

  

  

Date:

  

  

27 Oct 2013

 

  

  

Checked by:

  

  

JB

  

  

Date:

  

  

5 Nov 2013

 


  

  

  

  

  

 



2.4.5   Checking spare
parts 

If applicable, include a section in the IQ report on
change parts and list those that have 

been provided as part of the installation. These parts
need to be checked for compliance as described above in section 2.4.1. 




2.4.6   Checking
auxiliary equipment 

The installation may have ‘auxiliary equipment’
associated with it, which is not directly included in the scope of the IQ inspection.
An example might be a security and alarm 

system.
This equipment should be identified and listed in the IQ report. The report
should also include a description of the electrical, electronic or other
interfaces between this equipment and the installation itself. 

2.4.7   Checking information needed for the
preventive maintenance programme 

An effective preventive maintenance program (PMP) cannot
be implemented unless the relevant key elements are in place. The IQ inspector
should check the following: 

a.   Is all the
equipment and are all key components listed in the equipment inventory? 

b.   Are all these
items labelled in accordance with the organization’s equipment 

            management policies? 

c.   Is there an
equipment inventory file, and where is it located? 

d.   Is there a
maintenance logbook, and where is it located? 

All relevant documentation, drawings and installation
and commissioning records should be collected together in an equipment file
and attached to the IQ report. Table 5 shows one way to index this information
in tabular form. 

Table 5 - Equipment file index 




 


  

  

Information available in the equipment file

 

  

  




  

  

Equipment or

component ID

  

  




  

  

Equipment or

component name

  

  

TS

  

  

OI

  

  

MI

  

  

RS

  

  

Record type

  

  

Record number

 

  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




 


TS = Technical specifications   MI = Maintenance instructions 

OI = Operating instructions     RS = Recommended spare parts list 




2.4.8   Writing the IQ
report 

As soon as the IQ assessment has been completed, prepare
a report as outlined above in section 2.3.11. Pay particular attention to the
following points: 

•   Make sure that all of the sections included in
the IQ protocol have been completed, 

            signed and dated. 

•  
Record all deviations from the installation drawings and specifications
in the 

deviation report section. Make sure that each deviation
is cross-referenced to the relevant sections of the IQ protocol. 

•  
Specify the actions that need to be taken to correct the reported
deviations and 

            state the person or
organization responsible for completing these actions. 

•  
Transcribe any hand-written notes made by the IQ team into the relevant
sections 

            of the report. 

•   List
all members of the qualification team, and their designations. 







2.5   Operational qualification 

Do not begin the operational qualification stage until
all of the deviations recorded during the IQ inspection have been corrected. 

The purpose of operational qualification is
to establish that the installation and all its 

systems and sub-systems operate effectively and
consistently when the storage area is 

empty. As soon as the OQ process has
been completed and the installation has been 

approved, the next step is to carry on to the performance
qualification (PQ) stage, with the storage area full.  Once the entire OQ/PQ process has been
successfully completed, the installation can be signed off and fully released
for routine operation. 

An OQ inspection should cover the following points: 

•           Check the calibration of all temperature
measuring and controlling systems and 

components. 

•           Test the installation’s control systems and
check that these systems function 

correctly.  Check
the system set points. 

•           If there is a temperature alarm system, set
the low and high alarm limits and set up 

and test the relevant alarm outputs
such as email messages, SMS messages and telephone contacts.  Record the results. 

•           Carry out a temperature mapping of the empty
storage area and record the results. 

See Technical Supplement: Temperature mapping of storage
areas. 

•           Ensure that all relevant standard operating
procedures (SOPs) are available, that 

relevant personnel have been trained to follow these
SOPs and that training records are in place. 




2.5.1    Checking
installed systems, sub-systems and components 

As with the IQ procedure described in section 2.4.2, the
OQ inspection and test tables and 

report
should record the specified condition and the as found conditions and should 

confirm whether the as found condition is a pass or a fail. All deviations
should be 

recorded,
and the assessment results should be signed by the inspector and checked by 

the independent reviewer. 




2.5.2   Calibration of
controllers and sensors 

All the controllers and sensors that form part of the
installation should operate correctly 

and
have valid calibration certificates. These certificates should be attached to
the OQ 

report. Controllers and sensors should be suitably tagged so that they can be
identified. 

Each
tag should record the component ID, the calibration date and the calibration
expiry 

date.


The objectives of the inspection are to: 

•  
Check that all critical controllers and sensors have been calibrated and
that the 

            calibration status is current.


•  
Ensure that all these controllers and sensors are added to a calibration
and 

            preventive maintenance
programme. 

In order to meet the acceptance criteria, every critical
controller and sensor should have: 

•   A
current calibration certificate, with the certificate available. 

•   A
calibration that is traceable to national standards. 

•   An
attached calibration tag.

•   An
individual record in the calibration section of the preventive maintenance 

            programme. 




2.5.3   Standard
operating procedures 

There should be a comprehensive set of SOPs which cover
all relevant aspects of the installation, routine operation and
maintenance of the installation.  These
should be reviewed as follows: 

•  
Check that that all required SOPs have been written. 

•  
Check that their content relates to the actual installed equipment and
the specific 

            operational requirements of
the installation. 

•  
Check that a training programme is in place, based on the content of the
SOPs. The following acceptance criteria apply: 

•   All
SOPs must be approved and available. 

•   All
SOPs must be consistent with operational requirements. 

•  
There must be a training record, directly associated with each SOP, to
demonstrate 

            that training has been
conducted.. 

2.5.4  
Control panel 

The objective of the control panel inspection is to
establish that all temperature controls, indicators and other displays operate in
accordance with the manufacturer’s 

specifications. This inspection is equipment-specific and should be drawn up to
suit the system that has been installed. 

The acceptance criterion is that all these elements are
fully operational. 




2.5.5  
Alarm tests 

The purpose of the alarm tests is to confirming that the
alarm system operates in 

accordance with the design specifications. For
temperature alarm systems, there should be one high alarm test and one low alarm
test. If the system also has an event alarm system - for example a door open
alarm - this should also be tested. 

For each test, record the alarm settings and trigger the
desired alarm event. Confirm that 

the alarm system is activated. Activation may be indicated by an alarm sounder
or alarm 

strobe, by a signal to an alarm company which provides a remote monitoring
service 

(SaaS),
by SMS or telephone message or by any combination of these - all relevant
systems 

need
to be tested. 

Once the alarm tests have been completed, record the
results on an alarm system test sheet. A simple example is shown in Table
6.  More complex alarm systems will need
a more complex test sheet. Table 6 - Alarm system test sheet 




 


  

  

Alarm system test sheet

 

  

  




Test

  

  




Operation

  

  

Compliance

  

  

Deviation

report

number

  

  

Tested

by

  

  




Date

 

  

  

Yes

  

  

No

 

  

  

High temperature alarm

  

  

Alarm activated.

  

  




  

  




  

  




  

  




  

  




 

  

  

Low temperature alarm

  

  

Alarm activated.

  

  




  

  




  

  




  

  




  

  




 

  

  

High alarm setting:

  

  




 

  

  

Low alarm setting:

  

  




 

  

  

Checked by:

  

  




  

  

Date:

  

  




 


  

  

  

  

  

  

  

  

 



2.5.6   Temperature
mapping - empty 

The objective of the temperature mapping test is to
demonstrate that the installation is 

capable of controlling and maintaining a uniform
temperature when the storage area is 

empty. The complete area should be monitored for a
period of at least 24 hours using 

electronic data logging monitors (EDLMs). Table 7 shows
how the data should be recorded for an operational qualification test. 

Table 7 - Test data sheet: temperature distribution 




 


  

  




Data logger

ID number

  

  

Min. temp.

Recorded

(°C)

  

  

Max temp.

Recorded

(°C)

  

  

Mean

temp.

(°C)

  

  

Within range?

  

  




  

  




 

  

  

Yes

  

  

No

  

  

Inspected by

  

  

Date

 

  

  

DL-001

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-002

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-003

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-004

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-005

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-006

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-007

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-XXX

  

  




  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

Mapping period starts at (date/hour):

  

  




 

  

  

Mapping period ends at (date/hour):

  

  




 

  

  

Checked  by:

  

  




  

  

Date:

  

  




 


  

  

  

  

  

  

  

  

  

 






Note: The mapping procedure is fully described in the
companion Technical Supplement: Temperature mapping of storage areas. However,
in contrast to a full temperature mapping
exercise, mapping equipment for a qualification exercise only needs to be done
once. Table 7 is taken from Annex 1 of that supplement11.


2.5.7   Power failure
test 

The power failure test relies on the same data logger
setup as the temperature mapping test. The objective of the test sequence is
to establish and record: 

•   The
length of time during which the installation can maintain the specified 

temperature range following a power failure - this known
as the holdover time. 

•   How
long it takes the installation to recover within the specified range once power


            is restored. 

The results of these tests are simply recorded - there is
no deviation report. For cold 

rooms, freezer rooms and other large
temperature-controlled stores12 there are usually no set
acceptance criteria to be reached in this test. However, the test data are
useful for the store operator for emergency planning and
other purposes; for example, planning the 

installation and operation of standby generators. 

Power failure test: 

a.   Fixed power
failure period: In this version of the test the power is stopped for a 

predefined time period - for example, two hours -
regardless of whether or not the temperature inside the storage area exceeds
the required temperature range. 

Power
is then returned and the time taken for the storage area to recover within the
specified temperature range is measured. 

Because both these tests may trigger a temperature excursion,
carrying them out when the store is full of TTSPPs can place stored products at
risk. For this reason it is best carried out during operational qualification when the
store is empty.  Table 8 gives an example
of a power failure test sheet. 


























































11 The temperature mapping supplement
recommends that mapping should be carried out in both the hottest and coldest
months. However, for the purpose of operational qualification, only one mapping
exercise is required. 

12 In settings with unreliable electricity,
holdover is an important performance feature of mains 

powered freezers and refrigerators. For WHO prequalified
vaccine refrigerators, the holdover time is laboratory tested and reported. See the
WHO PQS website at: 

http://apps.who.int/immunization_standards/vaccine_quality/pqs_catalogue/ 







Table 8 - Power failure test sheet 




 


  

  




Data logger

ID number

  

  

Power off

Time temperature was

within
  range (hh:mm)

  

  

Power  on

Time to recover within

range (hh:mm)

  

  




Inspected by

  

  




Date

 

  

  

DL-001

  

  




  

  




  

  




  

  




 

  

  

DL-002

  

  




  

  




  

  




  

  




 

  

  

DL-003

  

  




  

  




  

  




  

  




 

  

  

DL-004

  

  




  

  




  

  




  

  




 

  

  

DL-005

  

  




  

  




  

  




  

  




 

  

  

DL-006

  

  




  

  




  

  




  

  




 

  

  

DL-007

  

  




  

  




  

  




  

  




 

  

  

DL-008

  

  




  

  




  

  




  

  




 

  

  

DL-009

  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-XXX

  

  




  

  




  

  




  

  




 

  

  

Power turned off at (hh:mm):

  

  




 

  

  

Power turned on at (hh:mm):

  

  




 

  

  

Checked  by:

  

  




  

  

Date:

  

  




 


  

  

  

  

  

  

  

 



2.5.8   Writing the OQ
report 

As soon as the OQ assessment has been completed, prepare
a report as outlined above in section 2.3.11. Pay particular attention to the
following points: 

•   Make
sure that all of the sections included in the OQ protocol have been completed, 

            signed and dated. 

•  
Record all deviations from the installation drawings and specifications
in the 

deviation report section. Make sure that each deviation
is cross-referenced to the relevant sections of the OQ protocol. 

•  
Transcribe any hand written notes made by the OQ team into the relevant
sections 

            of the report. 

•  
Specify the actions that need to be taken to correct the reported
deviations and 

            state the person or
organization responsible for completing these actions. 

•   List
all members of the qualification team, and their designations. 




2.6.1  
Checking installed systems, sub-systems and components 

As with the IQ procedure described in section 2.4.2 and
the OQ inspection in section 2.5.1, the PQ inspection and test tables and report
should record the specified condition and the as found conditions and should
confirm whether the as found condition is a pass or a fail. All
deviations should be recorded, and the assessment results should be signed by
the inspector and checked by the independent reviewer. 




2.6.2  
Temperature mapping - full 

The temperature mapping exercise described in OQ section
2.5.6 is repeated, but with the storage area normally loaded with TTSPPs.
The same arrangement of EDLMs should be used for the PQ mapping as for the OQ
mapping. 




2.6.3   Temperature
recovery after door opening 

The purpose of the door opening temperature recovery test
is to establish that the 

temperature within the store can return to the specified
temperature range within the 

specified
time following a door opening event. The following test parameters should be 

observed: 

•   The
same arrangement of EDLMs should be used as for the OQ and PQ mapping 

            tests. 

•   The
chosen door open period used for the test should represent actual door 

opening behaviour observed during routine operations. If
there is a single door, 

the critical factor is the maximum observed length of opening.  If there is more 

than
one door, the critical factors are the length of opening, the sequence of 

opening, and whether more than one door needs to be left
open at the same time. The acceptance criterion for this test is
that temperature recorded by all the EDLMs 

located inside the storage area should return within the specified temperature
range (e.g. 2°C to 8°C) within 30 minutes after the door(s) are closed at the
end of the door opening test sequence. Table 9 shows an example of a
door opening test sheet. 

Table 9 - Door opening test sheet 




 


  

  

Data logger

ID number

  

  

Time to return to within specified

temperature range

(min)

  

  

Compliance?

  

  




  

  




 

  

  

Yes

  

  

No

  

  

Inspected by

  

  

Date

 

  

  

DL-001

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-002

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-003

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-004

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-005

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-006

  

  




  

  




  

  




  

  




  

  




 

  

  

DL-007

  

  




  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




  

  




  

  




 

  

  

DL-XXX

  

  




  

  




  

  




  

  




  

  




 

  

  

Door(s) opened at (hh:mm):

  

  




 

  

  

Door(s) closed at (hh:mm):

  

  




 

  

  

Checked  by:

  

  




  

  

Date:

  

  




 


  

  

  

  

  

  

  

  

  

 






References 

•           Cloud, Phillip A. Pharmaceutical Equipment Validation: The Ultimate Qualification 

Guidebook. Interpharm Press, 1998. 

•           Health Canada (HPFB Inspectorate). Guide0001, Good Manufacturing Practices (GMP), Guidelines - 2009 Edition, Version 2. 

•           HealthCanada (HPFB Inspectorate). Guide 0069, Guidelines for temperature Control of Drug Products during Storage and

Transportation. October 17, 2005.

•           United States Pharmaceopaedia: Chapter 1079: Good Storage & Shipping Practices.

•           US Food & Drug Administration (FDA). cGMP Regulations 21 CFR part 210.

•           US Food & Drug Administration (FDA). cGMP Regulations 21 CFR part 211.

•           US Food & Drug Administration (FDA). cGMP Regulations 21 CFR part 820.

•           WHO Technical Supplement. Calibration of temperature control and monitoring devices.

•           WHO Technical Supplement. Temperature and humidity monitoring systems for fixed storage areas.

•           WHO Technical Supplement. Temperature mapping of storage areas.






Revision history 




 


  

  

Date

  

  

Change summary

  

  

Reason for change

  

  

Approved

 

  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




 

  

  




  

  




  

  




  

  




 








Annex 1 - Deviation and
corrective action report form 




 


  

  

Report Number:

  

  




 

  

  

DEVIATION DESCRIPTION

 

  

  




 

  

  

Documented by:

  

  

Date:

 

  

  

IMPACT ASSESSMENT ON QUALIFICATION

 

  

  

Does this deviation have sufficient impact on the
  qualification to require a

corrective action?

  

  

Yes

No

 

  

  




 

  

  

Documented by:

  

  

Date:

 

  

  

RATIONALE FOR CORRECTIVE ACTION

 

  

  




 

  

  

Documented by:

  

  

Date:

 

  

  

CORRECTIVE ACTION APPROVAL

 

  

  

Name

  

  

Signature

  

  

Date

 

  

  




  

  




  

  




 

  

  




  

  




  

  




 

  

  




  

  




  

  




 


  

  

  

  

 






 


  

  

RATIONALE FOR CLOSING THE DEVIATION REPORT

 

  

  




 

  

  

Does corrective action resolve the deviation?

(Attach all resulting test data sheets with this
  report)

  

  

Yes

 

  

  

No

Not applicable

  

  




  

  




 

  

  




 

  

  

Can this deviation be closed?

  

  

Yes

No

 

  

  

Name

  

  

Signature

  

  

Date