Equipment Qualification For RMG, FBD, Blender & Compression Machines

- An Overview
Validation is one of the important steps in achieving and maintaining the quality of the final product batch after batch. Without equipment, we cannot
manufacture a product. If equipment is validated, we can ensure that our product is of the best quality. Validation of the equipment is called the
Qualification. To manufacture different types of dosage forms, different equipments are used. Here, this article concentrates on the equipment
qualification for RMG, FBD, Blender & Compression Machine. It gives in detail, qualification steps of the equipment which is used for
manufacturing process through wet granulation
Keywords: Validation, Equipment Qualification, RMG, FBD, Blender & Compression Machines.
ABSTRACT
[1]
INTRODUCTION
In manufacturing facilities, validation test procedures are used to
validate equipment and processes that may influence product
quality. The tests for validation are used in accordance with
approved written qualification procedures.
All necessary activities and responsibilities for the qualification
and validation are controlled and specified in this Validation
Master Plan. Every step of the described validation program for
facilities, equipment, processes, process controls, and cleaning is
in accordance with the current European Community Guidelines
for GMP and FDA, and the cGMP guideline for finished
pharmaceutical manufacturers.
[2]
DEFINITION
Validation is documented evidence that provides a high degree
of assurance that a specific process will consistently produce a
product that meets its predetermined specifications and quality
attributes.
[2]
IMPORTANCE OF VALIDATION
Increased throughput
Reduction in rejections and reworking
Reduction in utility costs
Avoidance of capital expenditures
Fewer complaints about process-related failures
Reduced testing in-process and in finished goods
More rapid and reliable start-up of new equipment
Easier scale-up from development work
Easier maintenance of equipment
Improved employee awareness of processes
More rapid automation
[1,2]
TYPES OF VALIDATION
1. Retrospective validation
2. Prospective validation
3. Concurrent validation
4. Revalidation
Retrospective validation
Validation of a process for a product already in distribution, based
on accumulated production, testing, and control dates. Summary
of existing historical data.
The retrospective validation is used for facilities, processes, and
process controls in operation use that have not undergone a
formally documented validation process. Validation of these
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. Therefore, this
type of validation is only acceptable for well-established
processes and will be inappropriate where there have been recent
changes in the composition of product, operating processes, or
equipment. In each case of retrospective validation it must be
decided which elements of the validation life cycle (FIGURE 1)
should be used. In general, the design qualification is left out of
the retrospective life cycle.
The life cycle for retrospective validation is divided into the
following steps:
1. Actual survey of facilities, processes, and process
controls
2. Validation Master Plan (VMP)
3. Design Qualification (DQ)
4. Risk Analysis (RA)
5. Installation Qualification (IQ)
6. Operational Qualification (OQ)
7. Performance Qualification (PQ)
8. Process Validation (PV)
9. Cleaning Validation (CLV)
10. Computer Validation (CV)
11. Validation Report (VR)
12. Revalidation (ReV)
Prospective validation
Validation conducted prior to distribution either of a new
product, or a product made under a revised manufacturing
process. Validation is completed and the results are
approved prior to any product release.
Establishing documented evidence prior to process
implementation that a system does what it proposed to do based
on pre-planned protocols.
The life cycle for prospective validation is divided into the
following steps (FIGURE 2):
1. Validation Master Plan (VMP)
2. Design Qualification (DQ)
Satyabrata Jena *,K.Sravya, Arjun Goje, D. Narendra Prasad and Syed Sameer
Department of Pharmaceutics, Nalanda College of Pharmacy, Nalgonda, Andhra Pradesh,India.
Review International Journal of Novel Drug Delivery Technology
190
3. Risk Analysis (RA)
4. Installation Qualification (IQ)
5. Operational Qualification (OQ)
6. Performance Qualification (PQ)
7. Process Validation (PV)
8. Cleaning Validation (CLV)
9. Computer Validation (CV)
10. Validation Report (VR)
11. Revalidation (ReV)
Each prospective validation step will be described in
Qualification/Validation documents. In these documents, except
for the Validation Master Plan and the Validation Report, the test
methods for validation and acceptance criteria for the results are
specified. Also described are whether the equipment has to be
prepared for the test method and whether the original status of the
equipment has to be restored after testing.
Concurrent validation
It is a combination of retrospective and prospective
validation. Performed against an approved protocol but product is
released on a lot-by-lot basis. Usually used on an existing product
not previously validated or insufficiently validated.
Concurrent validation is used for establishing documented
evidence that a facility and processes do what they purport to do,
based on information generated during actual imputation of the
process.
The life cycle for concurrent validation is divided into the
following steps (Figure 3):
1. Validation Master Plan (VMP)
2. Design Qualification (DQ)
3. Risk Analysis (RA)
4. Installation Qualification (IQ)
5. Operational Qualification (OQ)
6. Performance Qualification (PQ)
7. Process Validation (PV)
8. Cleaning Validation (CLV)
9. Computer Validation (CV)
10. Validation Report (VR)
11. Revalidation (ReV)
Each concurrent validation step will be described in
Qualification/Validation documents. In these documents, except
for the Validation Master Plan and the Validation Report, the test
methods for validation and acceptance criteria for the results are
specified. Also described are whether the equipment has to be
prepared for the test method and whether the original status of the
equipment has to be restored after testing.
Revalidation
To validate change in equipment, packaging,
formulation operating procedure, or process that could impact
product safety, efficacy or potency. It is important to establish a
revalidation program for critical equipment to maintain validity.
[3,4,13,14]
EQUIPMENT QUALIFICATION
Qualification: Action of proving and documenting that
equipment or ancillary systems are properly installed, work
correctly, and actually lead to the expected results.
Qualification is part of validation, but the individual qualification
steps alone do not constitute process validation.
1 Design Qualification (DQ)
2 Installation Qualification (IQ)
3 Operational Qualification (OQ)
4 Performance Qualification (PQ)
5 Maintenance Qualification (MQ)
[3]
Design Qualification (DQ)
DQ defines the functional and operational
specifications of an instrument.
DQ defines the functional and operational specifications of the
instrument and details the conscious decisions made in the
selection of the supplier. DQ should ensure that instruments have
all the necessary functions and performance criteria that will
enable them to be successfully implemented for the intended
application and to meet user requirements.
The list below shows the recommended steps that should be
considered for inclusion in a Design Qualification:
Description of the analysis problem
Description of the intended use for the equipment
Description of the intended environment
Preliminary selection of the functional and performance
specifications (technical, environmental, safety)
Preliminary selection of the supplier
Final selection of the supplier and equipment
Development and documentation of final functional
and operational specifications
Vendor Qualification:
As part of the DQ process, the vendor should be
qualified; the question is how should this be done? Is an
established and documented quality system enough
(e.g. ISO 9001), or should there be a direct audit?
The answer is that there may be situations where a
vendor audit is recommended: for example, when
complex computer systems are being developed for a
specific user. However, this is rarely the case for
analytical instruments.
If equipment does not include a computer system, a
good reputation, one's own experience or good
references from other users together with ISO 9001
certification - can be sufficient.
[3]
Installation Qualification (IQ)
IQ ensures that an instrument is received as designed and
specified. It documents the installation in the selected user
environment.
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.
Before installation:
Obtain manufacturer' s recommendations for
installation site requirements
Check the site for the fulfillment of the manufacturer's
recommendations (utilities such as electricity, water and
gases plus environmental conditions such as humidity,
temperature, vibration level and dust).
Allow sufficient shelf space for the equipment itself,
related SOPs, operating manuals, logbooks and
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software
[3]
Operational Qualification (OQ)
OQ demonstrates that an instrument will function
according to its operational specification in the selected
environment.
Operational Qualification (OQ) is the process of demonstrating
that a instrument will function according to its operational
specification in the selected environment. Before OQ testing is
done, one should always consider, what the instrument will be
used for?. Testing may be quite extensive if the instrument is to be
used for all types of applications and where some of these place
great demands on the performance of the system.
[3]
Performance Qualification (PQ)
PQ demonstrates that a balance or instrument
consistently performs according to a specification appropriate to
its routine use.
Performance Qualification (PQ) is the process of
demonstrating that an instrument consistently performs
according to a specification appropriate to its routine use.
The test frequency is much higher than for OQ. Another
difference is that PQ should always be performed under
conditions that are similar to routine sample analysis
PQ should be performed on a daily (or at least a weekly)
basis, or whenever the instrument is used. The test frequency
depends not only on the stability of the equipment but also on
everything in the system that may contribute
to the analysis results.
1. Define the performance criteria and test procedures.
2. Select critical parameters.
3. Define the test intervals
[3]
Maintenance Qualification (MQ)
MQ describes and documents any maintenance required
on the equipment and includes the professional training of the
user.
The MQ describes and documents any maintenance
required on the equipment. This includes routine servicing and
any repairs necessary. Details of any maintenance contracts are
also documented in this section, together with a list of authorized
service engineers. In addition, the MQ includes the routine
cleaning of the equipment and also its ultimate disposal.
[2,8]
RAPID MIXER GRANUALATOR
1 Homogenous mixing of dry & wet powders,
deaaglomeration of wet mass and fast dispersion of
binding agent.
2 Dust free, high free flowing dosing particles, high
uniformity of granule size.
3 Frequency control for bottom driven Impeller Mixer
with 3 or 4 blades with exclusive scrape side design and
Chopper positioned to make granules.
The design of rapid mixer granulator is shown in the FIGURE 4.
Installation Qualification:
An IQ establishes confidence that the equipment is
properly installed. The installation must meet the
manufacturer's specified guidelines, along with design
changes at installation. Also the supporting electrical
utilities must meet all electrical codes.
Equipment identification:
Record the equipment identification number, with
equipment manufacturer, purchase order, model
number, equipment number.
Required Documentation:
The manufacturers operation and maintenance manual
and SOPs that cover the set up.
Utility requirements
Power
Water
Compressed air, spraying, impeller movement,
pneumatic discharge port.
Calibration Requirements:
Ammeter
Voltmeter
Water pressure gauge
Air pressure gauge
Equipment major specifications:
Mixing bowl material of contact, surface finishing,
dimensions, capacity.
Motors two are required
Discharge port
Lid
Liquid air dispersing system
Nozzle
Components coming in contact with product
Lubrication/ filter
Equipment Safety Features:
Emergency stop button, barrier guard, electrical inter
locking system, alarms
Control Functions:
regulators, discharge port opening, spraying button
Operational Qualification:
Calibration requirements for temp, timer, pressure
gauges, ammeter.
Equipment control functions:
Impeller, timer, bowl on/off & slow/fast buttons.
Emergency, discharge port on/off
Alarm, wash down walls on/off
Equipment operation:
On empty the impeller should run at low speed and also
check direction and speed.
Performance Qualification:
By using placebo max/min conditions are verified
[6,7]
FLUIDIZED BED DRYER
Design Qualification:
In FBD, the fluidizing air stream is introduced by a fan
or blower. The air is heated to the required temperature
in an air heater and flows upward through the wet
materials, which contained in a drying chamber fitted
with a wire mesh supported at the bottom.
Capacity : 5-200kg
Drying time : 20 to 40 min
The designs of the fluidized bed dryer are shown in the FIGURE 5
and Figure 6.
Installation Qualification
An IQ establishes confidence that the equipment is
properly installed. The installation must meet the
manufacturer's specified guidelines, along with design
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changes at installation. Also the supporting electrical
utilities must meet all electrical codes.
Verify approved purchase order.
Verify invoice.
Check manufacturer and supplier.
Verify model number and serial number.
Check for any physical damage.
Confirm location and installation requirements per
recommendation of manufacturer.
Verify that the utilities required are available.
Installation shall be conducted per instructions
provided in the manual.
Ensure that all relevant documentation is received:
User manual
Maintenance manual
List of change parts
Electrical drawings
Instruments for measuring temperature, humidity, time, air
volume and pressure, as well as recording devices
for these variables, should be calibrated.
Air temperature distribution
Place several thermocouples at different locations in an
empty fluid bed drier, e.g.:
Inlet air channel below product container mesh
bottom
Product container
Below filter bag
Above filter bag
Exhaust air channel
Measure the temperatures, letting in air of a constant temperature
(e.g., 60C).
Inlet air installation
Delay time for achieving constant air conditions
Determine, by use of a thermocouple and hygrometer,
the necessary delay time required at an adjusted inlet air
temperature (in relation to drying processes) for reaching
constant air conditions. Determine these figures for the first use of
the equipment at the working day, as well as for further use of the
equipment at the same working day.
Also calculate from the obtained data the water content of the
inlet air (g water per kg air) and compare with the previously fixed
requirements.
Microbiological quality of the inlet air
Determine, by use of a biotest RCS centrifugal air
sampler, the microbiological quality of the inlet air.
Sampling time 5 min = 8:1 air
Requirements
3
200 CFU/m inlet air
Influence of weather on inlet air conditions
Inlet air installation
Delay time for achieving constant air conditions
Procedure
Determine, by use of a thermocouple and a hygrometer, the
necessary delay time required at an adjusted inlet air temperature
(in relation to granulating processes) for reaching constant air
conditions. Determine these figures for first use of the equipment
at the working day, as well as for further use of the equipment at
the same working day.
Also calculate from the obtained data the water content of the
inlet air (g water/kg air) and compare to the requirements.
Equipment identification:
Record the
Equipment identification number
Equipment manufacturer
Purchase order
Model number
Equipment number
Required documentation:
v The manufacturers operation and maintenance manual
and SOPs that cover the set up.
Equipment Utility Requirements:
Compare the manufacturer's specified requirements to
their as found conditions at the time of qualification
testing.
Power
Steam
Compressed air
Calibration
Ammeter
Air/ water
Pressure gauge
Temperature gauge
Major component specifications:
Motor
Fan: mfg, location, no of blades, rotation, capacity
Ducting systems : material, type, welding, type of
welding, no of weld spots
Heater: voltage/ capacity
Air heaters: coils
Product container: housing, material, type of discharge
port.
Equipment Safety Features:
Barrier guard, alarm, emergency stop button, interlock
with housing, positive pressure differential with flow
regulators for fluid air regulation
Positive high temperature alarm device
Control functions:
Process control like temperature, timer on/off bath,
product discharge port buttons, filter bag, cleaning
button.
Operational Qualification
An OQ evaluation should establish that the equipment
can operate within specified tolerances and limits.
Verify alarm control.
Perform calibration requirements, identified in the
manual or established by the validation team.
Operate the equipment at low, medium, and high
speed per operations manual to verify the operating
control.
Verify that all switches and push buttons are
functioning properly.
Establish procedures for operation, maintenance, and
calibration.
Establish training program for relevant staff.
Procedure
Run three batches of each product and analyze for:
Active ingredient homogeneity
Moisture content
Particle size distribution
Percentage fines
Tap density
Based on these data try to fix a drying end point of the
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process (e.g., correlation between moisture content of the
product and the product bed temperature).
Calibration requirements:
All the critical instruments on the equipment must be
calibrated with calibration procedures. The equipments
calibrated are temperature probes, pressure gauges for
air/steam, timer, air flow rate and volume.
Equipment control functions
In this the ON/Off switches and discharge port are
verified and also the LED buttons.
Equipment Operation:
1. Drying cycle
2. Air flow
3. High temp
4. Filter test
5. feeding inlet/outlet
6. air volume
7. damper control
8. humidity control
9. drying time
All these parameters are recorded before operation
Performance Qualification
After the equipment proper installation it's functioning
and operating parameters must be verified.
Calibrated equipment like hydrometer, temp probes, air
flow monitors are required.
Using placebos the PQ is verified
The drying cycle parameters are fed charge at min &
max load.
As drying proceeds check temp, RH, fluidization
pressure, differential air pressure parameters, after
drying timer is set back to O to stop.
After drying the product check weight and also
sampling is done at varied time and location.
[1]
Test Functions
1. Perform Installation Qualification. Verify equipment
identification, required documents, utilities, manual,
and drawings.
2. Perform general operational controls verification testing.
Verify calibration requirements.
3. Operate system throughout the range of operating design
specifications or range of intended use. Verify switches
and push-buttons, open-door leaks, differential
pressure, timer operations, circulation air flow, exhaust
air flow, and high-temperature limit.
4. Verify that all safety devices are operating as specified in
the manual.
5. Verify that recommended lubricants are used during
machine operation.
6. Perform controller security challenges to verify that
specified parameters cannot be altered without
appropriate supervisory control.
7. Perform studies to check the moisture removal on each
product as per SOP.
8. Perform the study for establishing the drying time as per
acceptable moisture level.
[1]
Acceptance Criteria
1. The system is installed in accordance with design
specifications, manufacturer recommendations, and
cGMPs. Instruments are calibrated, identified, and
entered into the calibration program.
2. General alarms and controls operate in accordance with
design specifications.
3. The system operates in accordance with design
specifications throughout the operating range or range
of intended use.
4. The safety devices operate as specified in the manual.
5. The quality of lubricants is adequate, and their storage is
dry and cool.
6. Unauthorized changes to cycle parameters must not be
allowed without supervisory control or password.
7.The moisture level should meet specifications.
[13,14]
CONE BLENDER
The design of cone blender is shown in the Figure 7.
Installation Qualification:
Verify approved purchase order.
Verify invoice.
Check manufacturer and supplier.
Verify model number and serial number.
Check for any physical damage.
Confirm location and installation requirements per
recommendation of manufacturer.
Verify that the required utilities are available.
Installation shall be conducted per the instructions
provided in the manual.
Ensure that all relevant documentation is received:
User manual
Maintenance manual
List of change parts
Electrical drawings
Mechanical drawings
Calibration of the control and recording equipment:
Instruments for measuring temperature, pressure, time, mixing
chamber slope, and mixing velocity, as well as recording devices
for these variables, should be calibrated.
Operational Qualification:
Verify alarm control.
Perform calibration requirements, identified in the
manual or established by the validation team.
Operate the equipment at low, medium, and high
speed per operations manual to verify the operating
control.
Verify that all switches and push buttons are
functioning properly.
Establish procedures for operation, maintenance, and
calibration.
Establish training program for relevant staff.
Net capacity of the mixing chamber:
Procedure
Fill the mixing chamber with preweighed quantities of water.
Requirements
The available net capacity should be equal to the supplier
specification.
Mixing or stirring velocity:
Measure velocity three times at low, medium, and high speed and
compare the average and deviation from the average of the single
measurements with the supplier specification.
Requirements
Compliance with the supplier specification
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Performance Qualification:
Product homogeneity:
Mixing process:
Procedure: Fix the mixing or stirring velocity, load the mixer with
the product and switch the mixer on. After previously fixed
intervals, the mixer should be switched off and samples should be
taken from different locations of the product surface. The samples
should be analyzed for their active content.
Unloading:
Procedure: After determination of the suitable mixing time to
achieve product homogeneity, the influence of the unloading
process on the homogeneity should be evaluated. Samples should
be taken and sent to QC for analysis.
Requirements:
Homogeneity should remain consistent.
Water content of the product:
Take samples of the product prior to mixing, after mixing, and
after unloading (begin, mid, end). Determine the water content of
all samples.
[1]
Test Functions
1. Perform Installation Qualification. Verify equipment
identification, required documents, utilities, manual,
and drawings.
2. Verify components material.
3. Verify equipment safety features.
4. Operate the blender throughout the range of operating
design specifications or range of intended use.
5. Verify equipment switches, push-buttons, rotation
direction, and motor fixed speed.
6. Perform the assay to check the content uniformity on
blended granules at different locations.
[1]
Acceptance Criteria
1. The system is installed in accordance with design
specifications, manufacturer recommendations, and
cGMPs. Instruments are calibrated, identified, and
entered into the calibration program.
2. General alarms and controls operate in accordance with
design specifications.
3. The system operates in accordance with design
specifications throughout the operating range or range of
intended use.
4. The safety devices operate as specified in the manual.
5. The quality of lubricants is adequate and the lubricants
are properly stored.
6. Unauthorized changes to cycle parameters are not
allowed without supervisory control or password.
7. Assay results should be within the specifications.
[11,13]
TABLET COMPRESSION
VALIDATION OF A 45-STATION TABLET PRESS
The press is automatic, high speed rotary press. A motor
drives the press at speeds that vary from 410 to 1630 tablets per
minute (tpm). The material being tabletted is fed from a hopper by
gravity through the feed frame into dies. Regulating the weight
adjusting cam controls the weight of material in each tablet can be
adjusted.
The components of tableting equipment are shown in the
FIGURE 8.
Installation Qualification:
The IQ elements of a tablet press are shown in the
FIGURE 9.
The supporting electrical utilities must meet all electrical codes.
The information required for an IQ evaluation is equipment
identification, required documentation, equipment utility
requirements, major component specifications, component
material, lubricants and equipment safety features.
Equipment Identification:
Record the equipment identification numbers, along with the
following information:
Equipment manufacturer's purchase order number,
Model number
Serial number
Company assigned equipment number and
Location of the equipment
Required Documentation:
Record the equipment manufacturer's operation and maintenance
manual and drawings in Table 1.Record the SOP that cover the
setup, operation and cleaning of the tablet press in Table 2.

Equipment Utility Requirements:
Compare the manufacturer's specified volts (V) and amps (A)
requirements to their as-found conditions at the time of
qualification testing and record the results in the TABLE 3.Also
record the location of the power supply source. Record the
instrument used to measure the volts and amps in the Table 4.
Major Component Specifications:
The component specifications section of the protocol verifies that
the tablet press components purchased were delivered and
installed. Record the major components in the Table 5.
Component material:
Record the material of each component that contacts the product
in Table 6.
Lubricants:
Record the lubricants used to operate the tablet press in TABLE 7
and indicate if they make contact with the product.
Equipment Safety Features:
The objective of testing equipment safety features is to
verify that the safety features on the tablet press function
according to the manufacturer's specifications. This test is
performed with the tablet press empty. Verify that all of the guards
are present and record the results in the Table 8.
Operational Qualification
An OQ evaluation should establish that the equipment
can operate within specified tolerances and limits. The
mechanical ranges of the tablet press are challenged, along with
the basic tablet press operations. The tablet press will be validated
for its operating ability, not how well it makes tablets. Information
required for the OQ evaluation is: calibration of the instruments
used to control the tablet press, equipment control functions
(switches and push buttons) and equipment operation (cam
tracks, upper punches, lower punches, feed frames, take off bars,
rotor head direction, tablet press speed).The OQ elements of a
tablet press are shown in the Figure 10.
Calibration requirements
Verify that all the critical instruments on the equipment
have been logged into the calibration system, have calibration
procedures in place and are in calibration at the time of
qualification testing. Record all information for calibrated
instruments used to control the tablet press.
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Table 1: Manufacturer's Manuals and Drawings
Table 2: Standard Operating Procedures
Number Description Date
None Tablet press installation, operation and maintenance manual

Number Description Release date
TAB021 45- station tablet press and operation
TAB022 45- station tablet press cleaning procedure

Table 3: Utilities
Utility Specified Measured results Acceptable (yes/no)
Volts
Amps

Table 4: Instrument Used
Test instrument Identification number Calibration due date
Multimeter ME-025

Table 5: Major Components
Components As-found conditions
Tablet press motor Manufacturer:
Model number:
Serial number:
Volts :
Amperes :
Phases :
Cycles :
hp :
rpm
clutch Manufacturer :
Part number:
Serial number:

Table 6: Component Material
Component Material
Rotor head Mild steel
Hopper Stainless steel
Punches Mild steel
Dies Mild steel

Table 7: Lubricants
Where used Type Manufacturer Product contact
(yes/no)
Motor
Rotor bead gears
Punches and dies

Table 8: Safety Features And Test Results
Test function Expected results Acceptable (yes/no)
Gear guard Present and functional yes
Belt guard Present and functional yes
Upper punch guard Present and functional yes
Rear guard apron Present and functional yes
Clutch guard Present and functional yes
Splash guard Present and functional yes

Test function Expected results Acceptable
(yes/no)
Start switch operation When start switch is pressed, motor starts yes
Stop switch operation When stop switch is pressed, motor stops yes
Clutch lever operation When clutch lever is pushed clockwise, the clutch is engaged.
When clutch lever is pushed anticlockwise, the clutch is disengaged
yes
Safety adjusting wheel
operation
When safety moving adjusting wheel is turned, the pointer moves
up and down indicating compression force.
yes
Pressure adjusting
wheel operation
When the pressure adjusting wheel is turned, the pressure is
increased.
yes
Weight adjusting wheel
operation
When Weight adjusting wheel is turned, the lower punches are
lifted.
yes
Hand wheel operation When the hand wheel is turned, the rotor head rotates clockwise. yes
Motor adjusting wheel
operation
When the motor adjusting wheel is turned clockwise, the press
speed increases.
When the motor adjusting wheel is turned anticlockwise, the press
speed decreases.
yes

Table 9: Equipment Control Function Test Results
196
Figure 1: Retrospective Validation Life Cycle
Figure 2: Prospective Validation Life Cycle
Figure 4: Rapid Mixer Granulator Figure 3: Concurrent Validation Life Cycle
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Figure 6: Fluidized Bed Dryer
Figure 7: Cone Blender
Figure 8: Components Of Tableting Equipment
Figure 9: IQ Elements of a Tablet Press
Figure 10: OQ Elements of A Tablet Press
Figure 11: PQ Elements of A Tablet Press
198
Equipment Control Functions
The objective of testing equipment control functions is to verify
that the switches and push buttons on the tablet press operate per
the manufacturer's specifications. Record the results in the
TABLE 9. The tests will be performed with the tablet press empty.
Operate each control and verify its proper position.
Equipment Operation:
A) Cam Tracks Test
The objective of the cam track test is to verify that the upper
and lower cam tracks make contact with the upper punches
according to the manufacturer's specification. Use the
following procedure and record the results.
Install the punches and verify that the cams are
contacting the punch head angles on the both the
sides of the double-sided cams.
Verify that the punches are contacting one side
of the single-sided cam through a full cam track,
upper and lower.
B) Upper Punch Test
The objective of the upper punch test is to verify that the
upper punch penetration is according to the manufacturer's
specification. A vernier caliper is required for this test, which
is performed as follows:
Attach a piece of tape to mark the depth of
penetration of an upper punch when it is set to a
standard depth.
Remove the upper punch and use a calibrated
vernier caliper to measure the depth of penetration
into the die. Record the results and instrument used
to measure the depth.
C) Lower Punch Test
The objective of the lower punch test is to verify that the
lower punch height is set according to the manufacturer's
specification. A dial indicator test is required. Measure the
height of the lower punch above the die with a dial indicator
and record the results and the instrument used to measure the
height.
D) Feed Frame Test
The objective of the feed frame test is to verify that the feed
frame distance above the rotor head is according to the
manufacturer's specification.
Feeler gauge test: Measure the clearance between the feed
frame and the motor head with a feeler gauge and record the
results and the instrument used to measure the clearance.
E) Take Off Bar Test
The objective of the take off bar test is to verify that the take
off bars do not make contact with the lower punches. Turn the
tablet press by hand and verify that the takeoff bars do not
make contact with the lower punches. Record the results.
F) Tablet Press Rotation Direction
The objective of the rotation direction test is to verify that the
rotor head rotates in the proper direction. The tests will be
performed with the tablet press empty. Press the start switch
and observe the direction of the rotation of the rotor head as
viewed from front of the press and record the results.
G) Tablet Press Speed
The objective of the speed test is to verify that the measured
speeds are within 10 % of the manufacturer's specification
of a minimum of 9 rpm and a maximum of 36 rpm. This test
will be performed with the press empty. A stop watch is
required for this test.
Measure the speed of the rotor head with a calibrated
stopwatch. Verify that the measured speeds are within 10 %
of the manufacturer's specification and record the results and
the instrument used to measure the speed.
Performance Qualification
Once the equipment is properly installed and functioning
within is properly installed and functioning within specified
operating parameters, it must be shown that the tablet press
can operate reliably under routine, minimum and maximum
operating conditions.
The PQ elements of a tablet press are shown in the Figure 11.
Tablet weight and hardness
The objective of the weight and hardness test is to verify that
tablet weight and hardness can be maintained consistently
throughout the entire weight and hardness setting range.
The materials and instruments required for this test are a
placebo and a weight, hardness, and thickness gauge.
Compress tablets using a placebo granulation. Record the
placebo used. Obtain the average weight and hardness of 5
tablets at start up, 10, 20 and 30 min and record the results and
the instrument used to measure the weight and hardness.
[1]
Test Functions
1. Perform Installation Qualification.
2. Perform general operational controls verification testing.
3. Operate system throughout the range of operating design
specifications or range of intended use.
4. Verify that all safety devices of the tablet press are
operating as specified in the manual.
5. Verify that recommended lubricants are used during
machine operation.
6. Perform controller security challenges to verify that
specified parameters cannot be altered without
appropriate supervisory control.
7. Perform capability and consistency studies to check the
weight variation of each product as per SOP.
[1]
Acceptance Criteria
1. The system is installed in accordance with design
specifications, manufacturer recommendations, and
cGMPs. Instruments are calibrated, identified, and
entered into the calibration program.
2. General controls and alarms operate in accordance with
design specifications.
3. The system operates in accordance with design
specifications throughout the operating range or range of
intended use.
4. The safety devices must operate as specified in the
manual.
5. The recommended lubricants must be used as specified in
the manual.
6. The storage location of the lubricants must be according
to manufacturer recommendations.
7. Unauthorized changes to cycle parameters must not be
allowed without supervisory control or password.
8. The machine must be in statistical control as per
Int. J. Novel Drug Deliv. Tech.| Jul-Sep 2011 | Vol-1 | Issue-3
199
capability and consistency studies.
CONCLUSION
Allot extra time for validation. It always takes longer
than we think, particularly with a new installation.All phases of
validation successfully completed and final report signed
off.Review overall validation process and deviations to
determine how process could be handled better in the future. The
important points are: Carefully write protocols and acceptance
criteria, try to anticipate problems or issues in advance.
Coordination with other ongoing activities to ensure required
resources will be available when needed.Coordination with
vendors.Unless equipment qualification has not already been
legally mandated today, in the near future it will have overriding
importance, primarily in the pharmaceutical industry and in the
food and cosmetics sectors.
The main goal in qualifying laboratory equipment is to
ensure the validity of data. The current equipment qualification
programs and procedures used within the pharmaceutical
industry are based on regulatory requirements, voluntary
standards, vendor practices, and industry practices. The result is
considerable variation in the way pharmaceutical companies
approach the qualification of laboratory equipment and the way
they interpret the often vague requirements.
The state of equipment qualification practices in the
pharmaceutical industry is evolving and is subject to much
variation. Although more extensive guidance exists for
computerized systems than for noncomputerized components of
laboratory equipment, the additional validation requirements of
the computerized systems present many new challenges. Some
commercially available software may not completely meet
current requirements. A need exists for greater consistency in the
qualification and maintenance practices for common analytical
instruments used within the pharmaceutical industry. In today's
environment, there is a tendency to harmonize practices by
simply incorporating new procedures into existing programs. In
an atmosphere of growing regulatory expectations, this approach
is common but not recommended as a means of upgrading
qualification programs. The overall program should be evaluated
periodically to ensure that current requirements are met and that
excessive or inefficient practices are eliminated or changed.
Although variations in equipment qualification practices never
can be eliminated within the industry, it is recommended that the
industry be consistent in meeting core requirements.
REFERENCES
1. Syed Imtiaz Haider, Pharmaceutical Master Validation Plan:
the ultimate guide to FDA, GMP and GLP compliance, CRC
press, Florida; 2001
2. Syed Imtiaz Haider, Validation Standard Opreating
Procedures - A Step-by-Step Guide for Achieving
Compliance in the Pharmaceutical Medical Device and
Biotech Industry, CRC press, Florida; 2001
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4 . h t t p : / / w w w . a n a l y t i k -
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spx
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14.Kenneth W. Sigvardson, Joseph A. Manalo, Robert W. Roller,
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Int. J. Novel Drug Deliv. Tech.| Jul-Sep 2011 | Vol-1 | Issue-3
Received : 1 Aug 2011
Accepted :26 Aug 2011
Published:21 Sep 2011
Correspondence to
:Satyabrata Jena
E-mail: sbjena2007@gmail.com
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