1. Validation Of liquid Filling &
Sealing Machine
GGUUIIDDEEDD BBYY Presented by
DDrr.. KK.. KKiisshhoorree KKuummaarr V.RAJASHEKHAR
ROLL NO: 256213886028
1 September 30, 2014

2. Introduction
Equipment qualification:
 Action of proving that any equipment works correctly and actually
leads to the expected results.
 The equipment validation/qualification process generally covers
following steps..
2 September 30, 2014
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– User Requirement Specification (URS)
– Design Qualification (DQ)
– Installation Qualification (IQ)
– Operational Qualification (OQ)
– Performance Qualification (PQ)

3. Stages of Qualification
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4. • The previous figure depicts the most commonly used
approach to the qualification process as used in the
pharmaceutical industry.
• It shows a pyramid, which is the best way in which to
plan a qualification/validation project .
• Investing more time in the first phases will save time and
money in later and critical phases.
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5. Who Validation?should do
Equipment
• The vendor or the user ?
— User has the ultimate responsibility for the accuracy of
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the analysis results and also for equipment qualification.
— DQ should always be done by the user.
— While IQ for a small and low cost instrument is usually done
by the user, IQ for large, complex and high cost instruments
should be done by the vendor.
— OQ can be done by either the user or the vendor.
— PQ should always be done by the user because it is very .
application specific, and the vendor may not be familiar with
these
— PQ should be done on a daily basis.

6. Validation Of liquid
Filling Machine
6 September 30, 2014

7. Liquid Filling Machine
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 Liquid Filling Machines are specialized machines used
to fill bottles, vials, ampoules and other containers
with pre determined quantity of liquids.
 These machines are easy to operate and fill precise
quantity of liquid into containers.
 Filling equipment allow adjustment of different sized
bottles without changing parts.

8. Types of Liquid Filling Machines
 Volumetric Liquid Filling Machine :
Volumetric Fillers: Volumetric Liquid Filling Machines
are best suited for filling liquids with low to medium
viscosity.
 Vacuum Liquid Filling Machine:
Vacuum Fillers: Vacuum Liquid Filling Machines are
best suited for filling liquids that are foamy and caustic in
nature.
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9. 9
Vial filling&sealing machine

10. Ampoule filling&sealing machine
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11. Validation Protocol
• The entire process of equipment validation is
designed in the form of certain documented formats
or protocols.
• This helps in systematizing the study of equipment
validation.
• A validation protocol prepared by engineer or
validation specialist.
• The protocol sections contain required procedures
and forms.
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12. User Requirement Specification
 The user of the equipment has certain requirement
about the equipment which he wants to use
 Some of the general requirements may be stated in the
form of certain parameters like…
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– Size of equipment
– Speed of equipment
– Availability of spares, change part, immediate service at reasonable
– cLooswt sound generation
– Lesser breakdowns
– Materials of construction
– Auto control system
This requirements are generally discussed with the suppliers and based on
this discussion the selection of the equipment is done.

13. For example,
• In ampoule filling machine, a delivery tube provided for
repetitively forcing a measured volume of liquid through
the orifice of delivery tube designed to enter the
constricted opening of container.
• The size of delivery tube depend on ..
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– the opening of container
– the viscosity & density of liquid
– speed of delivery desired .

14. Equipment qualification:
 The equipment validation process generally
covers following steps..
– Design Qualification (DQ)
– Installation Qualification (IQ)
– Operational Qualification (OQ)
– Performance Qualification (PQ)
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30, 2014

15. Design Qualification and its
Certification
 If we are going to purchase an standard equipment then
the preparation of D.Q. dose not become very important
because we are accepting the manufacturer's design as it
is.
 However, if a particular equipment is to be fabricated as
per our requirements then the detailed D.Q. document
become very important and essential.
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16. Installation Qualification
 “Installation qualification establishes that the
instrument is received as designed and
specified, that it is properly installed in the
selected environment, and that this
environment is suitable for the operation and
use of the instrument”.
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17. • Installation Qualification involves,
– Verification of approved purchase order.
– Verification of invoice.
– Check manufacturer and supplier.
– Verification of model number and serial number.
– Checking for any physical damage.
– Confirm location and installation requirements as per
recommendation of manufacturers.
– Verify that the utilities required are available.
– Installation shall be conducted as per instructions provided in
the manual.
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18.  Ensure all relevant documentation is received like,
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− User manual.
− Maintenance manual.
− List of change parts.
− Electrical drawings.

19. Operational Qualification
• O.Q. is verification of performance of the system without load
• O.Q. section details the tests to be performed on the
equipment to document that it operates correctly
• O.Q. involve,
– Verification of alarm control.
– Perform calibration requirements identified in the manual or
established by the validation team.
– Operate the equipment at low, medium, and high speed as per
operations manual to verify the operating control.
– Verify that all switches and push buttons are functioning properly.
– Establish procedures (SOP) for operation, maintenance, and
calibration.
– Establish training program for relevant staff.
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20. Performance Qualification
• P.Q. is verification of performance of system with
load
• Filling studies will be run on all containers and fill
levels .
• The containers will be filled in triplicate runs .
• If a placebo is used, it should have similar physical
characteristics (viscosity, density, foaming) to the
actual fill materials.
• The study should be run at minimum, maximum and
intermittent speeds (in terms of ampoules/minute) .
• The filler must handle the containers without damage
and without jams.
• Accuracy and precision must meet specifications….
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21. Performance qualification of ampoule
filling and sealing machine involve,
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a) Wight variation test
b) Filling volume accuracy
c) Particle Contamination
d) Leaker test
e) Oxygen content

22. a) Weight variation test :
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– In the absence of specific criteria, weight variation
must conform to USP .
– In summary, all 10 units must be within 85.0 to
115.0% of target content, with a %RSD ≤ 6.0%, or
not more than 1 of the 30 units outside of the
85.0 to 115.0% and no units outside of 75.0 to
125.0%, with a %RSD ≤ 7.8%.

23. b)Filling Volume Accuracy:
The filling accuracy should be within ±% of the
adjusted and desired filling volume in
accordance with the machine specification.
eg.
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– Attention limit: ±1%
– Action limit: ±2%

24. c) Particle Contamination of Ampoules during
Filling & Sealing Procedure:
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– Ampoules should be filled with water for injection
and afterward be inspected on the contamination
with particles (particle classes: ≤10 μm and ≤25
μm).
– The inspection can be performed with a particle
counter.

25. d)Leaker test:
– Should capillary pore or tiny cracks be present, micro-organisms
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or other contaminants may enter the ampoule,
or the content may leak outside.
– Leaker usually detected by submerged ampoule in a deeply
colored dye solution (usually 0.5 to 1.0% methylene blue).
– Limitation is that capillaries of about less than 15 um not
detected by this method.
e) Oxygen content,
– If the filler produces a nitrogen purge, the
headspace gas should be analyzed for oxygen
content.

26. Requalification
• Requalification of systems and equipment should be done
in accordance with a defined schedule.
• The frequency of requalification may be determined on
the basis of factors such as the analysis of results relating
to calibration, verification and maintenance.
• There should be requalification after changes .
• The extent of requalification after the change should be
justified based on a risk-assessment of the change.
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