Transcript No Slide Title

3) Safety Considerations
Safety Overview
 Impart basic knowledge of pressure and the
forces exerted.
 Understand how temperature causes burn injury.
 Examples of Safety Incidents
 Understand Site Safety values and systems.
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Safety is a Value
 No
work should be started if it cannot be
completed safely.
 The goal is that personnel will go home as they
arrived - safe and without injury.
 Personnel should not be injured in the
manufacture of a product, which is designed to
improve the quality of life.
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Hazardous Process Safety
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Examples of Hazardous Processes Are:
Vessels (Pressurized)
 Plant steam (60psi, 150C)
 Clean steam (20-30psi)
 WFI (Water for Injection)
 Compressed air (95-105psi)
 CIP systems (~100psi, ~80C, CORROSIVE)
 Solution transfer lines
 Oxygen and nitrogen gas (& cylinders)
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Hazardous Process Safety
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Possible Hazards:
Impact from a blast or release of compressed liquid or
gas
 Traumatic injury from flying parts
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Burns from the release of hot liquid or gasses
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Contact with released liquid or gas (chemical burns)
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Fire resulting from the escape of flammable liquid or
gas (e.g. ethyl alcohol or oxygen leaks)
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Safety Considerations
Are you aware of the hazards of
pressure and temperature?
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Pressure Vessel Safety Considerations
This is a
processing
vessel…..
…..but its also
a time-bomb,
waiting to go
off in your
face.
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Pressure & Force
Can you get hurt with low pressure?
Lets review the details
Force = Pressure X Area
It’s like many small weights sitting
on a surface (area) which add up
to a large weight.
So at a given pressure,
The LARGER the area, The GREATER the
force
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Example 1
If Force = Pressure x Area, then, 14.5 psi pressure on a 12”
Diameter Sight Glass surface area will produce 1,640 pounds of
force. (Calculation: 14.5 x 3.14 x 62 = 1,639 lbs)
12”X Dia
Glass
12”
12” Sight
Square
14.5 psig
1 Bar
1,639 Pounds of Force
…this is equivalent to an object that weighs 1,639 lbs!
That's ~¾ of a Tonne (1 Tonne = 2205 lbs)
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Example 2
Again, Force = Pressure X Area, so:
24” X 24” Square Door
10 psig
(~0.7
Bar)
5,760 Pounds of Force
10 psi pressure on a 24”x24” square surface area (576 square inches)
is 5,760 pounds of force! (Calculation: 576 X 10= 5,760)
This is equivalent to an object that weighs 5,760 lbs.
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Example 3
Even with a few PSI say 3 PSI which may not be noticeable
on the Pressure gauge
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3 psig
6
80
2
40
8
150 Pounds of Force
120
lbf/in2
bar
10
8”XDia
Glass
12”
12”Sight
Square
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BE AWARE!
Can you get hurt with low pressure?
ABSOLUTELY !
Never underestimate the potential of a low pressure or vacuum
condition to cause damage.
….and be especially careful with large surfaces like
manways. 1 psi may not even register on the gauge but it’s
enough to send a hatch flying if the triclamp is removed and the
gasket is stuck.
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Low Pressure Hazard
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This door had the
equivalent of 1915 lbs of
force on it. And at only
2.8 psi.
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The door weighs about 15
pounds - much less than
the 1915 lbs of force on it.
When it came loose, it
slammed open seriously
injuring a person.
Over-Pressured Tank
This tank was fitted with:
 A high level alarm, which was accepted,
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and then forgotten
A pressure control system, which was
out of service
A pressure relief valve which was found
to be blocked
….so when the product was transferred
into the tank, it over pressured until the
roof ruptured, even though the pressure
was only a few psi over hydrostatic
Vacuum Safety
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The same concepts apply to
vacuum. However, in
vacuum systems the
pressure is pushing inward,
not outward.
Atmospheric Pressure
The pressure comes from
the atmosphere - we don’t
feel it but a tank does when
you pull vacuum on it.
Vacuum
Atmospheric Pressure (at sea level) is about 14.7 psi (1 Bar),
therefore full vacuum is -14.7 psi.
Vacuum Tank Hazards
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When the pressure inside the vessel is lower than atmospheric pressure,
the force acts inwards, with sometimes spectacular results….
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The tanker was being steam cleaned and, at the end of the job, the
hatches were closed. With no vacuum breaker fitted, as the steam
condensed, the tanker imploded…..
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Remember with a vacuum pulled, Hatches may appear stuck - venting to
Equalise Pressure, eases hatch removal. Never pressurise in an effort
to remove “Stuck Hatches”
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Covered Vent
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This tank collapsed while being pumped out!
Painters had covered the vent with plastic
sheeting. The steel tank collapsed before the
plastic sucked through.
Lack of Venting again
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This tank also collapsed while being pumped
out!
Follow the Correct procedure when
removing or opening vessel entry points
Always open
vent valves if
Possible
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When removing sight glass to make
chemical addition to water in media tank
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6
4
12
2
14
0
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Sight
glass
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18
10
bar
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Always open vent valves if possible, to ensure
Pressure Equalisation.
Check the pressure gauge reading first,
remember to eliminate “parallax error” from
your reading. Ensure pressure has not been
isolated at the regulator.
Never Pressurise a vessel to break a seal,
because at just a few PSI the subsequent
pressure release will be detrimental to property
or the person.
Projectile Hazards
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Unsecured gauges, valves,
and probes can become
“bullets” shot from tank
penetrations
Double check tightness before
adding pressure
Relieve pressure before
disassembling by Venting
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Hoses Drain Systems
Process Components
Sampling Points
Flailing Hoses
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Pressurised Hose connection that fails will
Flail.
Double Check tri-clamp connection before
adding pressure to hose.
Routinely check the condition of hoses for
any signs of bulging or failure.
A whipping line can break bones and
damage equipment,
If the line gets free leave the area
immediately and shut off flow to the line.
Never attempt to grab a whipping Line or
Hose.
Flexible hosing should be kept as short as
possible
Temperature, Burns and Scalds
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Hot WFI at 85 Degrees C
Clean Steam at 145 Degrees C
Both at Pressures between 6
Bar and 1.2 Bar.
High Risk of Scald injury from
hot spray or leak.
High risk of Burns from
surface of hot pipe work or
adjacent hot equipment.
First Degree Burn - Superficial
Involve the epidermis,
which appears pink or
red.
Are painful, don’t
blister and usually heal
within seven days,
without scarring.
Sunburn is usually a
first-degree burn.
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Partial Thickness - Second Degree Burns
Partial-thickness burns
involve the epidermis and
some of the dermis.
Deep partial-thickness
burns involve the
epidermis and deeper
extension into the dermis.
Protective ability of the
skin is lost.
Partial-thickness burns
are painful and appear
moist.
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Full Thickness – Third Degree Burns
Full-thickness burns involve
the epidermis, the entire
dermis and the
subcutaneous tissues.
They appear white or brown,
charred and leathery.
Not painful as they are deep
enough to have damaged the
nerve endings.
Are often surrounded by
painful partial-thickness
wounds.
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Incidents to take note of
Case #1:
 Case #2:
 Case #3:
 Case #4:
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Tank Light Incident
Production Support Sight Glass Accident
Operator Burn Incident
Manway opening at less than two Bar
Case # 1: Tank Light Incident
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Technician was removing tank
light (yellow arrow)
Technician did not check
pressure gauge first
Start-up engineers had
pressurized tank to 15 psi
Light fixture blew off, stopped by
pipe above. Sounded like
shotgun
Property damage only. Luck
‘prevented’ injury.
Case # 2: Production Support Sight Glass
Accident
Vent valve
closed
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Sight
glass
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Technician was removing sight
glass to make powder addition to
water in Buffer Tank
Technician did not check
pressure gauge first
Vent valve usually open, but had
been left closed by others from
prior activity; water addition
created 18 psi inside tank
Sight glass struck chin: 11
stitches and a broken tooth
Case # 3: Burn Incident
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The Technician was opening a
Drain Valve to empty a vessel
filled with 82oC WFI
The Clamp holding the Drain
Valve Failed allowing the hose
to disconnect.
The Operator was Sprayed
with Hot Water.
Case ## 3:
2 Operator
Burn Incident
Case
Burn Incident
The Technician:
 Failed to check hoses and clamps
 Misread pressure gauge before
opening the drain valve
 Didn’t wear proper PPE
Also:
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Training Aids Did Not Mention PPE
Requirements for the Job.
Poor arrangement of pressure
gauge and drain valve handle
contributed to the Technician
misreading the gauge.
Case # 4: Manway Opening at Less than
Two Bar
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The pressure in the vessel had
risen to 24.7 PSI (1.74 Barg)
during a routine operation.
Once the pressure reached 24.7
PSI, the tri-clamp was unable to
keep the manway in place and the
manway blew open, causing the
tri-clamp to hit and damage the
ceiling above.
Pressure acting on 12” Port
(Surface Area = 113 Sq. Inches)
Approx. 2,800 Pounds of Force
Case # 4: Manway Opening at Less than
Two Bar
Tri-clamp Deformation
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Hole in ceiling where tri-clamp
penetrated (6 ft up)
Case # 4: Manway Opening at Less than
Two Bar
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Failure occurred at a vessel pressure <2.0 Bar
A vent valve was programmed to open when the pressure
reached approximately 1.8 Bar
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This valve did not open.
Both of the clamp bolts were cut prior to use (To fit)
The bolt that failed was cut shorter than the other one
The Operator was unable to see how well the connection was
made as dome nuts covered the thread of the bolts
The Vessel was within normal operating pressures
The area was open to personnel
Safety Systems
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Tool Box Talks
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Safe Plan of Action
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Communications of Issues.
Link Productivity with Safety and Quality.
Incident communication and prevention.
Learn from mistakes.
Hazard review of the task.
Involve all involved in the task.
To be done on site while reviewing the hazard
Where a Safe Plan is carried out – Quality and productivity follow suite
Schedule Based Project – the risk
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Serious Injury or incident will affect the project
schedule.
Loss time due to:
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The Incident itself.
Personal loss to individual and family.
Incident investigation.
Investigation by H.S.A or Garda.
Closure of part of the project.
Loss of moral.
The list is endless…….
4) Validation
 Introduction
 What
requires validation?
 Pre Qualification Activities
 Stages of Validation
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What is Validation?
Ronseal Definition
 Proving with documented evidence that ‘Ronseal does
exactly what it says on the tin!!’…..
Sober Definition
 The purpose of validation is to establish documented
evidence which provides a high degree of assurance
that premises, facilities, equipment or processes have
been designed in accordance with the requirements of
current Good Manufacturing Practice (cGMP).
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What Areas Require Validation? All
systems or just cGMP systems
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Analytical and Quality Procedures
Instruments
Critical Support Systems (e.g. HVAC, WFI)
Raw Materials and Packaging
Equipment Design, Installation and
Operation
Facility Design, Installation and
Operation
Maintenance Systems
Manufacturing Processes
Product Design and Development
Control Systems
Qualification Activities
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GMP systems and equipment qualified through documented
challenge testing to verify that design intent and user requirements
have been met
GMP definition includes systems and equipment used in
manufacture, control, monitoring, storage and analysis of
pharmaceutical product
Where appropriate, documented successful pre-qualification
activities will be cited and referenced in lieu of repeating execution
steps in IQ (Installation Qualification) and OQ (Operational
Qualification)
IQ and OQ required for all GMP systems
PQ for critical utility and manufacturing equipment
Where do you start ?
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Validation Master Plan (VMP)
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Generally prepared for the start-up of a large project
Serves as both a guide to the Client and is used as a review
document for regulatory agencies
Develops concurrently with the project - a living document
Purpose of a VMP
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To briefly describe why, what, by whom, how and when the
validation is to be carried out.
Provide up-to-date information about the actual state of affairs
relating to validation
Demonstrate the companies commitment to carry out
validation
Pre-Qualification Activities
Purpose is to establish system / equipment
installation and functionality prior to commencing
formal qualification testing
 Steps include:
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Enhanced Design Review
 Factory Acceptance Testing (FAT)
 Commissioning
 Site Acceptance Testing (SAT)
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Example: Key Phases in a Project
Design &
Engineering
Construction
Cleaning Program phase 1
Start of
Development
Batches
Exhibit Batches
Complete
Cleaning Program phase 3
Process Validation
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Equipment
Commissioning
& Validation
Production
Process Trials
Cleaning Program phase 2
Stages of Validation
 Design Qualification (DQ)
 Installation Qualification (IQ)
 Operational Qualification (OQ)
 Performance Qualification (PQ)
 Process Validation (PV)
 Cleaning Validation (CV)
 Revalidation (RV)
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Design Qualification (DQ)
 Provides documented evidence that the
design/ quotation acceptance satisfies the
approved User Requirement Specification
(URS).
 Documenting that we are getting what we
asked for in our design i.e. Miele Dish
Washer capable of washing at temps from
25 to 80 Deg C, with air drying on a range
of dirty soils with detergent capability
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Installation Qualification (IQ)
 Provides documented verification that all key
aspects of the installation adhere to design
specification, regulatory and statutory codes and
manufacturers recommendations.
 Think of a dish washer at home. Checking vendor is
installing it correctly as per the
recommendations…Consider does this always go
well?!!
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Operational Qualification (OQ)
 Provides documented verification that the system
and sub-systems perform as intended throughout
all anticipated operating ranges.
 Think of dish washer again - Proving that it is capable of
running all of its cycles with process water in your
house and a range of detergents …drainability, spray
coverage etc
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Performance Qualification (PQ)
 Provides documented evidence that a GMP utility
service or process when operated or carried out
within defined parameters will consistently meet predetermined acceptance criteria. PQ will be performed
on those systems or processes that require
performance data for verifying proper operation.
 Proving that with Production materials, i.e. dirty plates, that it
will consistently clean to its pre defined criteria i.e. clean and
dry within an allocated time
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Performance Qualification (PQ)
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Challenge testing of performance under load conditions
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Challenge and establish performance ranges
 High
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& Low/ Min & Max
Challenge and establish conditions of operation
 Typical
environmental conditions
 Typical
working volumes
 Typical
run durations
Sampling test plan
Integration of automated control systems and individual units
Media Simulation
 Important step of aseptic processing
 Demonstrates that the process, equipment, people and
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utilities when operating together are capable of reliably
producing sterile product.
Bacteria friendly food (Media) is processed through all of
the equipment as a challenge. A simulation is likely to
include the following steps
 Media compounding
 Sterilisation of the media by filtration
 Filling
Cleaning Validation (CV)
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Program designed to ensure that equipment can be
cleaned to a pre-defined cleaning acceptance criteria to
ensure that any carryover of product does not affect the
strength, purity, identity, quality or safety of the
subsequent product
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Limits for cleaning based on toxiciology of product in
body, and consider the risk of transferring small
amounts of 1 product into another.
Cleaning Validation (CV)
Cleaning Cycles
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Focus on efficacy of set parameters
Validate on “worst case” basis, and provide added level of
assurance of efficacy in actual operation
Execution of process parameters monitored with each execution
Cleaning validation will address operations performed between
campaigns of different products
Cleaning validation will address operations performed between the
manufacturing of batches of the same product
Process Validation (PV)
Irrespective of product, Process Validation is preceded by a
formal, documented development phase:
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Run media runs and hold studies
Complete transfer / validation of test methods
Challenge process and manufacturing equipment set points, ranges and
durations
Evaluate efficacy of equipment cleaning processes
Re-establish in-process product hold intervals
Finalization and approval of manufacturing process and batch record
Evaluate comparability of development batches to licensed material
Process Validation (PV)
General Requirements of Process Validation:
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Can be based on successful validation and approval of the products
at other licensed sites
Minimum of three production batches
Evaluate manufacturing operations using qualified facilities and
equipment train, under typical processing conditions
Confirm stability of product through established expiry period
Demonstrate reproducible manufacturing process capable of
meeting pre-determined quality attributes
Verify shipping conditions and product impact resulting from
shipment to regional packaging facility
Demonstrate consistency with product specifications
Process Validation (PV)
Example: Drug Product Manufacturing Validation will focus on:
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Demonstrating ability to maintain established environmental and aseptic
conditions throughout the manufacturing process
Maintaining all equipment settings within established ranges
Confirm performance of the formulation process
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Evaluation of product transfer steps:
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 Filling line:
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Set up
Speed
Filling duration
Consistency across batch
Capping system operation:
Crimping
Vial track
Revalidation (RV)
 The action of providing documented evidence that equipment
and ancillary systems continue to operate within predetermined and specified ranges and continue to meet user
needs as established through validation testing. This is
accomplished by performing planned Revalidation testing,
performing Periodic Review and, where deemed necessary,
Revalidation testing as a result of the conclusion from the
Periodic Review performed.
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Ensuring on a periodic basis that the dish Washer is still working. The
worst case washing cycle would be run and documented i.e. does you
dish washer work consistently !!
Documentation Practices
Types of Documents
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Procedures/ Protocols for
DQ/IQ/OQ/PQ Cleaning and
Process Validation
Reports summarising the
validation studies providing
conclusion to validated status of
equipment
Deviations : raised when certain
tests acceptance criteria cannot
be met. These need to be
investigated and closed out prior
to Validation summary report
approval.