A
seminar
On
Validation Of Ampoule Filling &
Sealing Machine
Department Of Quality
Assurance
Maliba Pharmacy
College
10 April 2015
1
Introduction
• Validation may be defined as,
“The documented act of demonstrating that
any procedure, process, and activity will
consistently lead to the expected results
which includes the qualification of systems
and equipment”
10 April 2015
2
Continued….
• The equipment validation process generally
covers following steps..
–
–
–
–
–
User Requirement Specification (URS)
Preparation of Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)
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3
Stages of Qualification
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 should do Equipment Validation?
• The vendor or the user ?
— User has the ultimate responsibility for the accuracy of
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
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6
Validation of
Ampoule Filling &
Sealing Machine
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7
10 April 2015
8
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9
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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Continued….
• The procedure describe “how” the system is to
be validated, while the forms document these
procedure and provide a written record of the
performed qualification and validation processes
• Each protocol package is divided into three
section:
– Installation qualification (IQ)
– Operational Qualification (OQ)
– Performance Qualification (PQ)
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11
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…
– Size of equipment
– Speed of equipment
– Availability of spares, change part, immediate service at
reasonable cost
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Continued….
–
–
–
–
Low 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
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Continued….
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 ..
– the opening of container
– the viscosity & density of liquid
– speed of delivery desired
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14
Preparation of D.Q. 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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Continued….
• It is advisable to work out the detailed
equipment specifications by sitting together
with the equipment manufacturer
• It may also be advisable to perform Factory
Acceptance Test (FAT) at the manufacturer’s
premises before dispatch of the equipment to
the purchaser
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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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Continued….
• The 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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Continued….
• Ensure all relevant documentation is received
like,
−
−
−
−
User manual
Maintenance manual
List of change parts
Electrical drawings
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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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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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• P.Q. of ampoule filling and sealing machine
involve,
a)
b)
c)
d)
e)
10 April 2015
Wight variation test
Filling volume accuracy
Particle Contamination
Leaker test
Oxygen content
22
a)Weight variation test :
– 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%
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Continued…..
b)Filling Volume Accuracy:
The filling accuracy should be within ±% of the
adjusted and desired filling volume in
accordance with the machine specification.
eg.
– Attention limit: ±1%
– Action limit: ±2%
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Continued….
c) Particle Contamination of Ampoules during
Filling & Sealing Procedure:
– 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.
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Continued….
d)Leaker test:
– Should capillary pore or tiny cracks be present,
micro-organisms 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.
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Continued….
e) Oxygen content,
– If the filler produces a nitrogen purge, the
headspace gas should be analyzed for oxygen
content
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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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References...
1) R. A. Nash & A. H. Wachter, “Pharmaceutical process
validation”; Third edition
2) Leon Lachman, H. A. Lieberman & J. L. Kanig, “The
Theory and Practice of Industrial Pharmacy”; Third
edition, Pg. No. - 667 to 674
3) Manohar A. Potdar, “Pharmaceutical Quality
Assurance”, Pg. No.- 8.13, 8.14
4) Syed Imtiaz Haider, “Validation Standard Operating
Procedure”, Pg. No. - 304 to 307
5) Syed Imtiaz Haider, “Pharmaceutical Master
Validation Plan”, Pg. No. – 140
6) http://www.validationworld.com/
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