validation of equipment

1. 1
Sneha A. Chavan
M- Pharmacy 1st Year, I
Semester

2. USFDA, 1987
 A Documented programme, which provides a high degree of assurance
that a specific process will consistently produce, a product meeting its
pre-determined specifications and quality attributes.
 validation is scientific study of process :
1. To prove that process is consistently doing what it is suppose to do
(i.e., the process is under control)
2. To determine the process variables and acceptable limits for these
variables, and to set up appropriate in – process controls.
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3.  Reduction of quality cost ( less reject, rework, wastage and so on)
 Assurance of quality
 Safety
 Government regulation
 Validation is necessary part of a quality assurance program and is
fundamental to efficient production operation.
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 Stage 1 – Process Design: The commercial process is defined during
this stage based on knowledge gained through development and scale-
up activities.
 Stage 2 – Process Qualification: During this stage, the process design
is confirmed as being capable of reproducible commercial
manufacturing.
 Stage 3 – Continued Process Verification: Ongoing assurance is
gained during routine production that the process remains in a state of
control.
Stages Of Process Validation

5.  A Documented programme which provides a high assurance
that a specific process will consistently produce a product,
meeting its pre-determined specification and quality attributes.
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6.  Validation team consist of following departments
• Involve with new or modified equipment
or facilities
2.Engineering
• Whose process require validation3. Production
• Concerning change control4. Maintainance
• Involve with the testing laboratories5. Quality Control
• Involve with GMP compliance6. Quality Assurance
• Involve with new product development
and new product improvement
1.Research operation
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Team Work

7. Totally new
processes.
New equipment.
Process where the
end product test is
poor and unreliable
indicator of product
quality.
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8. Validation Programme
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 Define objective
 Type of validation
 Type of process
 Define the process ( chart or flow diagram of the process)
 Defination of process output ( in terms of potency or yield)
 Analysis of process ( critical process and variables)
 Control limits of critical variables
 Preparation of validation protocol ( details about facilities, sampling,
test to perform, methods used )
 Organizing for validation ( define responsibilities of each department)
 Planning validation trial
 Validation trials ( supervision, administration, documentation)
 Validation finding ( data, summery, analysis, conclusion)
 Final report and recommendations ( process validated further trials)

9. Prospective validation
Concurrent validation
Revalidation
Retrospective Validation
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PROSPECTIVE
VALIDATION
CONCURRENT
VALIDATION
RETROSPECTIVE
VALIDATION
REVALIDATION
Establishing
documented
evidence prior to
process
implementation that
a system does what
it proposed to do
based on
preplanned
protocols
Monitoring of
critical processing
steps and end
product testing of
current production,
to show that the
manufacturing
process is in a state
of control.
Validation of
facilities,
processes, and
process controls is
possible using
historical data to
provide the
necessary
documentary
evidence that the
process is doing
what it is believed
to do.
It means repeating
the original
validation effort or
any part of it, and
includes
investigative review
of existing
performance data.
Process for a new
formula (or within a
new facility) must
be validated before
routine
pharmaceutical
production
commences.
This is conducted in
a product already
distributed based
on accumulated
data of production,
testing and control.
maintain the
validated status of
mfg processes

11. Reason For Revalidation
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 Changes in the starting material(s)
 Change of formulae.
 Changes in the packaging material.
 Changes in the process.
 Changes in equipment.
 Changes in the production area and support system.
 Unexpected changes.

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 Additionally, the following points should be checked at the time of a
scheduled revalidation:
 Have any changes in master formula and methods, batch size, etc.,
occurred? If so, has their impact on the product been assessed ?
 Have calibrations been made in accordance with the established
programme and time schedule ?
 Have the standard operating procedures (SOPs) been properly
updated ?
 Have the SOPs been implemented ?
 Have the cleaning and hygiene programme been carried out ?
 Have any changes been made in the analytical control methods ?
Cont…

13. VALIDATION OF SOLID
DOSAGE FORM
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15.  Both Active Pharmaceutical Ingredients (APIs) And Excipients
 Product Variation Or Deviation From Specification.
 Stability Of The Product.
 Compatible With The Other Ingredients
 The individual supplier’s conformance to regulatory requirements in
terms of facilities, personnel, operating procedures, and controls.
 water content, residue on ignition, and heavy metals, should also be
monitored
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Validation Of Raw Material

16. Cont…
 Manufactured in different grades and by different companies.
 Differences in the chemical composition, crystallinity, and particle size/size
distribution between different lots.
 Besides differences can be seen with the same company using different
manufacturing sites, raw materials, and/or manufacturing processes.
 Differences in particle size distribution between lots can result in:
(1) the initial mix not actually being uniform
(2) materials segregating during compression.
 A smaller particle size – more binder solution - granules having greater
strength - decrease the tablet dissolution rate.
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on-site inspection
of the supplier to
review the vendor’s
manufacturing
operations and
control procedures
If it is in acceptable
range of
specifications and
stability, it should
be used to
manufacture a
batch of the final
dosage form
Assessme
nt of raw
material
stability
Performing checks
on several batches
(at least three)
from the primary
supplier as well as
the alternate
supplier.
Validation Of Raw Materials -
Steps

18.  A wet granulation formulation may require two mixing/ blending steps:
(1) prior to granulating to have a uniform drug/excipient mixture, and
(2) after milling the dried granulation to add other excipients, such as the
lubricant.
 Factors in creating a uniform mix or blend:
1. Bulk density
2. Particle shape
3. Particle size distribution
4. Surface area
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Validation Of Mixing / Blending

19. Cont….
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Mixing or
blending
technique
Mixing or
blending
speed
Mixing or
blending time
Drug
uniformity
Excipient
uniformity
Equipment
capacity/load:

20. Validation Of Granulation
 type of wet granulation technique
 Will it be low shear (e.g., Hobart), high shear (e.g., Diosna, GEI-Collette) OR fluid
bed (e.g., Glatt, Fluid Air)?
 Each technique will produce granules with different physical properties and will
require monitoring of different processing parameters.
 Wet granulation parameters to be considered during development and validation
are:
 Binder addition
 Binder concentration
 Amount of binder solution/granulating solvent
 Binder solution / granulating solvent addition rate
 Mixing time
 Granulation end point
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21. Validation of liquid
dosage form
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24. VALIDATION OF
SEMISOLID DOSAGE
FORM
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25. Validation Parameter For Semisolid Dosage
Form
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 Addition of wax depend on its melting point
 Mixing speed
 Mixing time
 Temperature
 Cooling time
 Homogenizing speed
 Homogenizing time
 Filling machine speed
 Product temperature to aid product flow and maintain product
consistency before and during filling and packaging operations

26. Validation of Parenteral
Dosage form
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27. Filling
 System currently used in parenteral filling include
1.Positive displacement volumetric liquid filler
2.Time –Pressure Filling
3.Weight Dosing Filling
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28. Validation condition
1. viscosity
2. Type of product e.g., (Non-aqueous product, suspension)
3. Design of filling needles for high-speed filling equipment.
4. Filling system
5. Fill volume accuracy
6. Fill the product without splashing, foaming or damaging the container
7. Factor affecting fill volume accuracy are
a) Machine speed ( depend on machine design)
b) Delivery system pressure
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29.  Inspection performed by three technique
Visual inspection
with manual
handling
Visual inspection
with automated
handling
Automated
inspection
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Validation of inspection

30. Validation Condition
 Trained visual inspector
 monitored by an in-process testing group
 Operating speed of presentation device based on normal defect level
present in those operation.
 If defect level higher than normal, so machine can be slowed to allow
removal of all defective units.
 excessive spin rate will create bubble, which will result in false reject
 An insufficient spin rate may not adequate suspend particles in liquid.
 Variability in light intensity will cause signal fluctuation that will
interpreted as reject by detection device.
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31. Validation of
Equipment
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32. Equipment qualification
 Equipment qualification phase of certification involves the assessment
of the equipment that will involved in the certification against the
purchase specifications or any other equipment requirement that exit.
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33. Parts of Equipment Validation
Equipment
Validation
Installation
Qualification (IQ)
Operational
Qualification (OQ)
Performance
Qualification (PQ)
Design
Qualification (DQ)
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Design
qualification (DQ)
defines the
functional and
operational
specifications of
the instrument
and details for
the conscious
decisions in the
selection of the
supplier
Installation
qualification(IQ)
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
Operational
qualification (OQ)
is the process of
demonstrating
that an
instrument will
function
according to its
operational
specification in
the selected
environment
Performance
Qualification (PQ)
is the process of
demonstrating
that an
instrument
consistently
performs
according to a
specification
appropriate for
its routine use

37. Validation of Mixer/granulator
a. Method of mixing (e.g., planetary, pneumatic)?
b. Is the equipment capable of providing low and/or high shear to the
material?
c. Can the mixing be varied (e.g., changing the rpm of the impeller)?
d. Does the mixer/granulator have a monitoring system (e.g., end point
detection) or can it accommodate one?
e. What is the working load range and capacity of the equipment?
f. How is material charged and discharged from the unit? Is it manual,
semi automated, or automated?
g. Are there options to introduce the granulating fluid (e.g., dump,
meter, or spray)?
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a. What is the operating principle of the dryer (e.g., direct heating—fluid
bed, indirect conduction—tray, or indirect radiant—microwave)?
b. Will the wet material be static (e.g., tray) or fluid (e.g., fluid bed)?
c. What is the working load range and capacity of the equipment?
d. What is the heating range and airflow capabilities of the equipment?
e. What is the heat distribution of the unit? Are there any hot and/ or
cold spots?
f. Temperature
Validation Of Dryer

39. Validation Parameters For Tablet Coater
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 Tablet properties
 Equipment type
 Coater load
 Pan Speed
 Spray Guns
 Application/Spray rate
 Degree of Atomization &
Spray Pattern
 Tablet flow
 Inlet/outlet temperature and
airflow
 Coating solution
 Coating weight
 Residual solvent level

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41. Seminar Open For Discussion
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