Prepared by Pradnesh P Sandikar (545)

VALIDATION OF EQUIPMENT: VALIDATION OF TABLET COMPRESSION

(MACHINE)

CONTENT :-
Definitions,
General Introduction of Qualifications,
Introduction of Compression machine,
Installation Qualification Compression machine (IQ)
Operation Qualification Compression machine (OQ)
Performance Qualification Compression machine (PQ)
Validation Protocol of Compression machine
Definitions :- 1
) Validation :
Establishing documented evidence with provides a high degree of assurance
that a specific process will consistently produce a product meeting its pre-
determined specifications and quality attributes.
2) Calibration :
The process quantitatively defining system responses to known controlled
signal output.
Purpose of Validation : Purpose of Validation Method is suitable for its
intended purpose to get consistent, reliable and accurate data. Identification of
Sources and Quantization of Potential errors Satisfy FDA Requirements
Establish Proof that a Method Can be Used for Decision Making Advantages:
Advantages Increased output Reduction in rejections and reworking cost
effective.
Avoidances of capital expenditures Reduced testing in-process and in finished
goods Easier maintenance of equipment.
When should be validated :
Change in established method New method developed for a particular
problem Established method used in different laboratories, different
equipment or different staff Out-of-control situations within internal quality
assurance Demonstration of equivalence between two methods (e.g. a rapid
new test against a standard method)
General Introduction Of Qualifications Qualification:
The action of proving that any equipment Works correctly and leads to the
expected results.
INSTALLATION QUALIFICATION:
The equipment installation is the qualification of equipment as it is to be
installed.
This qualification involves the coordinate efforts of the vender, the operating
department, and the Project team that will provide input into the purchase,
installation, operation and the maintenance of the equipment.
Once the prequalification is completed, the efforts move to owner’s plant. The
Installation area should be reviewed to verify that it is in accordance with the
specification.

Figure1: Installation qualification elements

1. The approved purchase order should be
verified. 2. The invoice check manufacturing
and supplier should be verified.
3. The model and the sequential number should
be verified.
4. If there any physical damage should be
checked.
5. To fit in with the area and establishment
prerequisite as per the suggestion of the
producer
6. Check that the ideal utilities are accessible.
Installation qualification establishes of
confidence that the instrument was properly
installed. And the installation have to meet the
producers identified guidelines as well as the
design variations at installation. The material is
involved for an installation qualification evolution
is instrument identification, utilities, document
requirements, major component specification,
material component, lubrication, specification.
Compression is a critical step in the production of a
tablet dosage form. The materials being
compressed will need to have adequate flow and
compression properties. Factors to consider during
compression are as follows: i)Tooling
ii)Compression speed Overall Dimension - Measure
with measuring tape
RPM of turret (max. & min.)
-Check by tachometer Hopper Conventional hopper
- by visually check MOC (Material of construction) -
Using Molybdenum Kit Height - Measure with
measuring tape.
No. of station - Visually count no. of holes on turret
Type of tooling - Using Venire caliper check the die
hole diameter Turret MOC – by visual check
Circumference –Measure with measuring tape
Distance between two dies
Using Venire caliper Feeder - by visual check Main
electrical motor HP – Visually check by reading plate
affixed on motor RPM - Visually check by reading
plate affixed on motor or Direction of motor (anti
clockwise) - by visual check Required Utilities i )
Electricity - by visual check
Thickness controller cam
Weight controller cam
Emergency switch
Dust Extraction and exhaust System Main drive
Available ON Indicator
By visual Potentiometer check Selector switch
Emergency OFF button
Lubrication Oil pressure gauge Selector switch for
Auto/ Manual.

Identification of equipment

Record the identification instrument number, as well

as the following, required information:
Equipment purchase order number, Serial number
of the equipment, Model number, The company
allocated instrument number and The area of the
instrument.

Documentation requirements

Record the manufacturer’s operation instrument,

manual preservation and designs. Collect the
standard operating procedures that protect the
operation, setup, and tablet compression cleaning.

Required utilities

The equipment utility requirements is to contrast

the producers specified amps (A) & volts (V), as the
requirements are found the specification at the
period of testing for the qualification and record the
results. And also, record the areas were current
supply source present.

Major component specification

It is a part of the procedure, make sure that the

tableting compression elements were purchased,
installed & delivered. Major components were
recorded.
Component material

Each component of the material was recorded and

that the components contact the product in the table
1 below.
Table 1: Component material

Components Materials
Dies Mild steel
Punches + Stainless
steel
Hopper Mild steel Head
of the rotor Mild steel
Lubricants

It should be recorded and is used to carry out the

tableting equipment. Specify if they make a
connection with the result.

Instrument safety characteristics

The safety features of tablet press functioning

according to the producer’s requirements are
considered as the objectives for testing equipment
safety features. The test is been carried out with the
empty tablet press in order to check whether all of
the guards are present and record the results.
2) OPERATION QUALIFICATION:

On completion of installation of the equipment at the

final processing site and of the installation
qualification document, a complete equipment
operation qualification must be performed. The
equipment operation qualification protocol should
describe all aspects of the testing of equipment in
detail.
1. The alarm control should be verified.
2. The calibration requirements should be performed
and identified by the validation team
3. The equipment should be operated at lower
medium speed and higher medium speed as per
the manual operation to prove the
operations switches. 4. Whether all the
pushbuttons and switches are working properly
and should be verified.
5. When the procedure should be initiated for
calibration, operation, and maintenance.
6. Organize a training program for relevant
employees.
7. Start at least one pilot batch for every product
Figure 2: Operational qualification elements
The operation qualification evaluation must initiate
that the instrument can perform within the specified
limits & tolerances. The OQ mechanical series of the
tablet press is challenged, together with the
fundamental tablet press processes. The tableting
equipment should be confirmed for its working
capacity, not how nicely it makes drugs. The
information is involved for an operation qualification
evaluation is calibrated of the equipment having
already been used to restrict the tableting press,
instrument control function (push buttons& switches)
& operation of the equipment (upper punches, lower
punches, cam tracks, tablet press speed, take-off
bars, feed frames, rotor head rotation direction).
Operational qualification check list:

1) Compare the all specification and write the

observation Main Switch – Check visually by
operating the main switch of the machine. 2) Start
push button – (illuminated Green switch) By
pressing start button the Green switch glows and the
main drive motor should start.
3) Stop push button - (illuminated red switch) By
pressing stop button the red switch glows and the
main drive motor should stop.
4) Turret RPM challenge test set in digital table
counter by rotating knob Check by tachometer
Rotation direction ( clock wise) by visual check
5) Emergency switch (Machine should be stop)
6) Selector/ isolator switch (Machine start/stop) 7)
Tablet thickness Visually & Hardness controls
check By turning the swing lever to right
(anticlockwise) thickness increased/ hardness
decrease vise versa.
8 ) Tablet weight controls Dozer and wedge is
moved clockwise Decrease / increase / Anti
clockwise weight
9) Machine speed adjustment Release the locking
knob and rotate increased speed / the hand
wheel anticlockwise / clockwise decreased speed
10) Main upper punch entry Remove the bolt and
rotate the upper punch penetration Perforated
Segment to Right / Left increase / decrease 11)
Agitator controller i)Turn the agitator ON - Check by
tachometer ii) Turn the knob and set the 5 RPM

Calibration requirements

All equipment instrumentation should be verified and

has to log into a calibration system, while
qualification, calibration should be on time and
procedure of the calibration is to in place. The
information on calibrated equipment is to be
recorded and control the tableting equipment.

Equipment control functions

Verify the testing instruments and the equipment

push buttons & switches on the equipment work
according to the producer requirements and
specification. The test will be conducted with the
empty tablet press.

Equipment process
Cams Track Test

The objective test is to make sure that the superior

cam tracks test and inferior cam tracks test is a
direct connection with upper punches following to
the processer requirements. And the following
methods are used and the result should be
recorded. The punches are installed to check
whether the cams are make contact with the punch
head angles on both parts of the double-sided cams.
The punches are verified to check whether they are
make contact with one side of the single-sided cam
through a full cam track, including upper and lower
cam.

Upper Punches Test

Verify that the upper punch test and upper punch

perforation is matching to the producers
requirements. The Vernier caliper equipment is used
for the upper punch test and the following
performance: Connect the part of the tape and to
point the intensity of penetration of the upper punch
when this test is set towards a standard depth.
The standardized Vernier caliper is used to estimate
the penetration intensity into the dies. The upper
punch should be removed and results should be
recorded.

Lower Punches Test

Verify the actual of its lower punch and that the

height of the lower punches is to set the accord into
producer specification. This test is required for dial
indicator and measure the lower punch height with
that dial indicator and results were recorded.

Feed Frame

The purpose of this test should be verified and this

test distance upper the rotor head is matching to the
producer specification. In this test, the feeler gauge
is mainly required. And to estimate the approval
between the rotor head and feed frame with the
feeler gauge.

Take-off Bar Test

Verify that the Take-off bar test and it do not connect

with the inferior punches and turn the tableting
equipment by using hand and the take-off bar
should not connect with the punches. Results should
be recorded.

Equipment Rotation Direction

The equipment rotation direction check is to verify

the head of the rotor is rotates inside the right
course. The test might be achieved with an empty
tablet press. And start the equipment by pressing
start buttons and observe the route of the rotation of
the head of the rotor as considered from the front of
the tablet press

Tablet press speed

To measure the speeds are within the +/-10% of

manufacturers specification of a minimum of 9rpm
and maximum of 36rpm. It will be conducted with the
empty press. The Id of the stopwatch is needed for
the tableting equipment test. A calibrated stopwatch
is used to estimate the speeds of the rotor head.

3) PERFORMANCE QUALIFICATION:
This phase will see the engineering function coming
to a close with the various engineering and
validation sign offs.
The validation function will allow the project to move
closer to final close-out and transfer of the entire
project to the project coordinator or operating
department E.g. validation of sterile area. To check
the instrument is installed properly and then
performing in the specified operating parameters.
The equipment can work reliably under minimum,
maximum & routine working conditions. Evaluation
of compression characteristics of tablet &
capabilities. The compression characteristics of
tablet & capabilities: Thickness, Hardness, weight
variation, Content uniformity, Disintegration time and
Friability.
Figure 4: Performance Qualification elements

Performance Qualification Objectives

Starting 3 products of biliary and compressed the

one layer batches by using a compression machine.
During the performance, qualification is to check all
the critical parameters of the result.
Measure the thickness, hardness, friability, and
weight for each triplicate tablet run, as shown above
figure 4.

PQ checklist:
 Compare all description and enter the remark of all
three batches. 1. Brand name
2. Average weight (20 tablets)
3. Batch number
4. Size (Batch)
5. Weight of the individual tablet
6. Description of product
7. Rotation per minutes (machine)
8. Thickness (mm)
9. Hardness (kg/cm2)
10. Punch Shape
11. Punch diameter
12. Upper punch and lower punch.

Operation

Tablet Hardness test & Weight

Verify that the hardness and weight of the tablet
should be consistently maintained throughout the
complete hardness and weight of the tablet setting
range.
1. The equipment’s & materials are used for this
test are a placebo and weight, hardness and
thickness gauge.
2. The tablets are compressed by using a placebo
granulation.
3. Average weight & hardness of the 5 tablets at
startup, 10, 20, & 30 minutes, & Record the result.
4. The equipment is mainly used to measure the
hardness and weight of the tablet and record the
results.

Speed test

1. The speed test was recording the functioning of

the equipment using a placebo.
2. The objectives are also to confirm the
equipment can preserve consistent tableting speeds
during the speed range for tableting.
3. Calculated & recorded the equipment variable
speeds.
4. A placebo test, a stopwatch, and a scale this
test materials & equipment is required.
5. The tablets should be compressed then
applying for placebo granulation. The average
weight and hardness of the 5 tablets at startup, 10.
20 and 30 minutes & record the result.

VALIDATION PLAN AND METHODOLOGY

Performance of the Double Rotary Tablet Compression Machine shall be tested

at extreme and optimum operation conditions, which are identified as Critical
Process Variables:-
Critical Process Variables are:
• Machine Speed (RPM)
• Percentage Occupancy of powder level in hopper
• Pre Compression force

Equipment Performance Qualification shall be carried out, simulating actual

production conditions and varying minimum and maximum critical process
variable conditions. No Pharmaceutical Active Ingredients shall be used for the
qualification purpose. Excipients used for manufacturing of routine products
using Compression method shall be used for the study.

Dispensing, sifting and blending of the raw material and finally compression of
the blended powder shall be done. Physical characters of the powder blend (i.e.
Bulk Density, tap Density, Compressibility ratio and particle size analysis) are to
be recorded from three different layers of blend, unloaded from blender to
ensure the physical uniformity.

VALIDATION MATRIX

Validation Plan is described in the following Matrix:

Process Parameter Numbe Number of Quality Samplin g

Variable selected for r of tablets to Parameter frequenc
qualificatio trials be s to be y
n compresse tested
d

Effect of 16 01 5000 a. Weight 3 set of

Machine variation sample
Speed 32 01 5000 containin g
b. Hardnes 50 tablets
48 01 5000
s in each
(RPM of the
trial
Machine) (Total:
c. Thickne 50´3=15
ss 0 Tablets)
 d. Friability

Effect of 20% 01 5000 a. Weight 3 set of

powder variation sample
level in 50% 01 5000 containin
hopper g 50
80% 01 5000
tablets in
(% each trial
Occupancy (Total:
50´3=15
0 Tablets)
of powder
in the
hopper)

Effect of Nil 01 5000 a. Hardnes 3 set of

Pre- s sample
Compressio Optimum 01 5000 containin
n Pressure b. Thickne g 50
Maximum 01 5000 ss tablets in
each trial
(Total:
50´3=15
0 Tablets)

ACCEPTANCE CRITERIA
• Average weight variation of tablets should not be more than ±2% of
target weight and individual weight variation should not be more than
±5% of target weight.
• Hardness of tablets should not be less as per prior fixed specification
• .
• Friability should not be more than 1%.
• Relative Standard Deviation between the results of any test parameters
should not be more than 5%.

RE-VALIDATION CRITERIA
Performance Qualification of Double Rotary Tablet Compression Machine
to be Re-validated on:
• Substitution of existing Tablet Compression Machine with a new Tablet
Compression Machine.
• Replacement of existing instrument / component with a new one, which
can have a direct impact on the performance of the Tablet Compression
Machine.
• Any major modification to the existing Tablet Compression Machine
which can affect the performance of the equipment.
• If the Tablet Compression Machine is found to be malfunctioning during
performance qualification.