International Journal of Novel Drug Delivery Technology Review

Equipment Qualification For RMG, FBD, Blender & Compression Machines

- An Overview
Satyabrata Jena *,K.Sravya, Arjun Goje, D. Narendra Prasad and Syed Sameer

Department of Pharmaceutics, Nalanda College of Pharmacy, Nalgonda, Andhra Pradesh,India.

ABSTRACT
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.

INTRODUCTION [1] formally documented validation process. Validation of these

In manufacturing facilities, validation test procedures are used to facilities, processes, and process controls is possible using
validate equipment and processes that may influence product historical data to provide the necessary documentary evidence
quality. The tests for validation are used in accordance with that the process is doing what it is believed to do. Therefore, this
approved written qualification procedures. type of validation is only acceptable for well-established
All necessary activities and responsibilities for the qualification processes and will be inappropriate where there have been recent
and validation are controlled and specified in this Validation changes in the composition of product, operating processes, or
Master Plan. Every step of the described validation program for equipment. In each case of retrospective validation it must be
facilities, equipment, processes, process controls, and cleaning is decided which elements of the validation life cycle (FIGURE 1)
in accordance with the current European Community Guidelines should be used. In general, the design qualification is left out of
for GMP and FDA, and the cGMP guideline for finished the retrospective life cycle.
pharmaceutical manufacturers.
DEFINITION[2] The life cycle for retrospective validation is divided into the
Validation is documented evidence that provides a high degree following steps:
of assurance that a specific process will consistently produce a
product that meets its predetermined specifications and quality 1. Actual survey of facilities, processes, and process
attributes. controls
IMPORTANCE OF VALIDATION[2] 2. Validation Master Plan (VMP)
• Increased throughput 3. Design Qualification (DQ)
4. Risk Analysis (RA)
• Reduction in rejections and reworking 5. Installation Qualification (IQ)
• Reduction in utility costs 6. Operational Qualification (OQ)
• Avoidance of capital expenditures 7. Performance Qualification (PQ)
• Fewer complaints about process-related failures 8. Process Validation (PV)
• Reduced testing in-process and in finished goods 9. Cleaning Validation (CLV)
• More rapid and reliable start-up of new equipment 10. Computer Validation (CV)
• Easier scale-up from development work 11. Validation Report (VR)
• Easier maintenance of equipment 12. Revalidation (ReV)
• Improved employee awareness of processes
• More rapid automation Prospective validation
TYPES OF VALIDATION [1,2] Validation conducted prior to distribution either of a new
1. Retrospective validation product, or a product made under a revised manufacturing
2. Prospective validation process. Validation is completed and the results are
3. Concurrent validation approved prior to any product release.
4. Revalidation Establishing documented evidence prior to process
implementation that a system does what it proposed to do based
Retrospective validation on pre-planned protocols.
Validation of a process for a product already in distribution, based The life cycle for prospective validation is divided into the
on accumulated production, testing, and control dates. Summary following steps (FIGURE 2):
of existing historical data.
The retrospective validation is used for facilities, processes, and 1. Validation Master Plan (VMP)
process controls in operation use that have not undergone a 2. Design Qualification (DQ)

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3. Risk Analysis (RA)
2 Installation Qualification (IQ)
4. Installation Qualification (IQ)
5. Operational Qualification (OQ) 3 Operational Qualification (OQ)
6. Performance Qualification (PQ) 4 Performance Qualification (PQ)
7. Process Validation (PV) 5 Maintenance Qualification (MQ)
8. Cleaning Validation (CLV)
9. Computer Validation (CV) Design Qualification (DQ)[3]
10. Validation Report (VR) DQ defines the functional and operational
11. Revalidation (ReV) specifications of an instrument.
DQ defines the functional and operational specifications of the
Each prospective validation step will be described in instrument and details the conscious decisions made in the
Qualification/Validation documents. In these documents, except selection of the supplier. DQ should ensure that instruments have
for the Validation Master Plan and the Validation Report, the test all the necessary functions and performance criteria that will
methods for validation and acceptance criteria for the results are enable them to be successfully implemented for the intended
specified. Also described are whether the equipment has to be application and to meet user requirements.
prepared for the test method and whether the original status of the The list below shows the recommended steps that should be
equipment has to be restored after testing. considered for inclusion in a Design Qualification:
• Description of the analysis problem
Concurrent validation
• Description of the intended use for the equipment
It is a combination of retrospective and prospective • Description of the intended environment
validation. Performed against an approved protocol but product is • Preliminary selection of the functional and performance
released on a lot-by-lot basis. Usually used on an existing product specifications (technical, environmental, safety)
not previously validated or insufficiently validated. • Preliminary selection of the supplier
Concurrent validation is used for establishing documented
evidence that a facility and processes do what they purport to do, • Final selection of the supplier and equipment
based on information generated during actual imputation of the • Development and documentation of final functional
process. and operational specifications
The life cycle for concurrent validation is divided into the Vendor Qualification:
following steps (Figure 3):
1. Validation Master Plan (VMP) As part of the DQ process, the vendor should be
2. Design Qualification (DQ) qualified; the question is how should this be done? Is an
3. Risk Analysis (RA) established and documented quality system enough
4. Installation Qualification (IQ) (e.g. ISO 9001), or should there be a direct audit?
5. Operational Qualification (OQ) • The answer is that there may be situations where a
6. Performance Qualification (PQ) vendor audit is recommended: for example, when
7. Process Validation (PV)
8. Cleaning Validation (CLV) complex computer systems are being developed for a
9. Computer Validation (CV) specific user. However, this is rarely the case for
10. Validation Report (VR) analytical instruments.
11. Revalidation (ReV) • If equipment does not include a computer system, a
Each concurrent validation step will be described in good reputation, one's own experience or good
Qualification/Validation documents. In these documents, except references from other users – together with ISO 9001
for the Validation Master Plan and the Validation Report, the test
certification - can be sufficient.
methods for validation and acceptance criteria for the results are
specified. Also described are whether the equipment has to be Installation Qualification (IQ)[3]
prepared for the test method and whether the original status of the IQ ensures that an instrument is received as designed and
equipment has to be restored after testing. specified. It documents the installation in the selected user
environment.
Revalidation IQ establishes that the instrument is received as designed and
To validate change in equipment, packaging, specified, that it is properly installed in the selected environment,
formulation operating procedure, or process that could impact and that this environment is suitable for the operation and use of
product safety, efficacy or potency. It is important to establish a the instrument.
revalidation program for critical equipment to maintain validity. Before installation:
· Obtain manufacturer's recommendations for
EQUIPMENT QUALIFICATION [3,4,13,14]
installation site requirements
Qualification: Action of proving and documenting that · Check the site for the fulfillment of the manufacturer's
equipment or ancillary systems are properly installed, work recommendations (utilities such as electricity, water and
correctly, and actually lead to the expected results.
Qualification is part of validation, but the individual qualification gases plus environmental conditions such as humidity,
steps alone do not constitute process validation. temperature, vibration level and dust).
1 Design Qualification (DQ) · Allow sufficient shelf space for the equipment itself,
related SOPs, operating manuals, logbooks and

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software • Record the equipment identification number, with

Operational Qualification (OQ)[3] equipment manufacturer, purchase order, model
OQ demonstrates that an instrument will function number, equipment number.
according to its operational specification in the selected Required Documentation:
environment. — The manufacturers operation and maintenance manual
Operational Qualification (OQ) is the process of demonstrating and SOPs that cover the set up.
that a instrument will function according to its operational • Utility requirements
specification in the selected environment. Before OQ testing is • Power
done, one should always consider, what the instrument will be • Water
used for?. Testing may be quite extensive if the instrument is to be • Compressed air, spraying, impeller movement,
used for all types of applications and where some of these place pneumatic discharge port.
great demands on the performance of the system. Calibration Requirements:
Performance Qualification (PQ)[3] • Ammeter
• Voltmeter
PQ demonstrates that a balance or instrument
• Water pressure gauge
consistently performs according to a specification appropriate to
• Air pressure gauge
its routine use.
• Equipment major specifications:
Performance Qualification (PQ) is the process of
• Mixing bowl material of contact, surface finishing,
demonstrating that an instrument consistently performs
dimensions, capacity.
according to a specification appropriate to its routine use.
• Motors two are required
The test frequency is much higher than for OQ. Another
• Discharge port
difference is that PQ should always be performed under
• Lid
conditions that are similar to routine sample analysis
• Liquid air dispersing system
PQ should be performed on a daily (or at least a weekly) • Nozzle
basis, or whenever the instrument is used. The test frequency • Components coming in contact with product
depends not only on the stability of the equipment but also on • Lubrication/ filter
everything in the system that may contribute Equipment Safety Features:
to the analysis results. • Emergency stop button, barrier guard, electrical inter
1. Define the performance criteria and test procedures. locking system, alarms
2. Select critical parameters. Control Functions:
3. Define the test intervals • regulators, discharge port opening, spraying button
Operational Qualification:
Maintenance Qualification (MQ)[3]
• Calibration requirements for temp, timer, pressure
MQ describes and documents any maintenance required
gauges, ammeter.
on the equipment and includes the professional training of the
• Equipment control functions:
user. • Impeller, timer, bowl on/off & slow/fast buttons.
The MQ describes and documents any maintenance • Emergency, discharge port on/off
required on the equipment. This includes routine servicing and • Alarm, wash down walls on/off
any repairs necessary. Details of any maintenance contracts are Equipment operation:
also documented in this section, together with a list of authorized • On empty the impeller should run at low speed and also
service engineers. In addition, the MQ includes the routine check direction and speed.
cleaning of the equipment and also its ultimate disposal. Performance Qualification:
RAPID MIXER GRANUALATOR [2,8] By using placebo max/min conditions are verified
1 Homogenous mixing of dry & wet powders,
deaaglomeration of wet mass and fast dispersion of FLUIDIZED BED DRYER [6,7]
binding agent. Design Qualification:
2 Dust free, high free flowing dosing particles, high • In FBD, the fluidizing air stream is introduced by a fan
uniformity of granule size. or blower. The air is heated to the required temperature
3 Frequency control for bottom driven Impeller Mixer in an air heater and flows upward through the wet
with 3 or 4 blades with exclusive scrape side design and materials, which contained in a drying chamber fitted
Chopper positioned to make granules. with a wire mesh supported at the bottom.
The design of rapid mixer granulator is shown in the FIGURE 4. • Capacity : 5-200kg
Installation Qualification: • Drying time : 20 to 40 min
• An IQ establishes confidence that the equipment is The designs of the fluidized bed dryer are shown in the FIGURE 5
properly installed. The installation must meet the and Figure 6.
manufacturer's specified guidelines, along with design Installation Qualification
changes at installation. Also the supporting electrical • An IQ establishes confidence that the equipment is
utilities must meet all electrical codes.
Equipment identification: 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 Equipment identification:
utilities must meet all electrical codes. Record the
· Verify approved purchase order. Equipment identification number
· Verify invoice. Equipment manufacturer
· Check manufacturer and supplier. Purchase order
· Verify model number and serial number. Model number
· Check for any physical damage. Equipment number
· Confirm location and installation requirements per Required documentation:
recommendation of manufacturer. v The manufacturers operation and maintenance manual
· Verify that the utilities required are available. and SOPs that cover the set up.
· Installation shall be conducted per instructions Equipment Utility Requirements:
provided in the manual. • Compare the manufacturer's specified requirements to
· Ensure that all relevant documentation is received:
their as found conditions at the time of qualification
· User manual
testing.
· Maintenance manual
• Power
· List of change parts
• Steam
· Electrical drawings
• Compressed air
Instruments for measuring temperature, humidity, time, air
• Calibration
volume and pressure, as well as recording devices
• Ammeter
for these variables, should be calibrated.
• Air/ water
Air temperature distribution
Place several thermocouples at different locations in an • Pressure gauge
empty fluid bed drier, e.g.: • Temperature gauge
· Inlet air channel below product container mesh • Major component specifications:
bottom • Motor
· Product container • Fan: mfg, location, no of blades, rotation, capacity
· Below filter bag • Ducting systems : material, type, welding, type of
· Above filter bag welding, no of weld spots
· Exhaust air channel • Heater: voltage/ capacity
Measure the temperatures, letting in air of a constant temperature • Air heaters: coils
(e.g., 60°C). • Product container: housing, material, type of discharge
Inlet air installation port.
Delay time for achieving constant air conditions Equipment Safety Features:
• Barrier guard, alarm, emergency stop button, interlock
Determine, by use of a thermocouple and hygrometer, with housing, positive pressure differential with flow
the necessary delay time required at an adjusted inlet air regulators for fluid air regulation
temperature (in relation to drying processes) for reaching • Positive high temperature alarm device
constant air conditions. Determine these figures for the first use of Control functions:
the equipment at the working day, as well as for further use of the • Process control like temperature, timer on/off bath,
equipment at the same working day. product discharge port buttons, filter bag, cleaning
button.
Also calculate from the obtained data the water content of the Operational Qualification
inlet air (g water per kg air) and compare with the previously fixed An OQ evaluation should establish that the equipment
requirements. can operate within specified tolerances and limits.
Microbiological quality of the inlet air · Verify alarm control.
· Perform calibration requirements, identified in the
Determine, by use of a biotest RCS centrifugal air manual or established by the validation team.
sampler, the microbiological quality of the inlet air. · Operate the equipment at low, medium, and high
Sampling time 5 min = 8:1 air speed per operations manual to verify the operating
Requirements control.
200 CFU/m3 inlet air · Verify that all switches and push buttons are
Influence of weather on inlet air conditions functioning properly.
Inlet air installation · Establish procedures for operation, maintenance, and
Delay time for achieving constant air conditions calibration.
Procedure · Establish training program for relevant staff.
Determine, by use of a thermocouple and a hygrometer, the Procedure
necessary delay time required at an adjusted inlet air temperature Run three batches of each product and analyze for:
(in relation to granulating processes) for reaching constant air · Active ingredient homogeneity
conditions. Determine these figures for first use of the equipment · Moisture content
at the working day, as well as for further use of the equipment at · Particle size distribution
the same working day. · Percentage fines
Also calculate from the obtained data the water content of the · Tap density
inlet air (g water/kg air) and compare to the requirements. 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.
Test Functions[1]
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.
Acceptance Criteria[1]
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
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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.
CONE BLENDER[13,14]
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

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.
Test Functions[1]
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.
Acceptance Criteria[1]
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.
TABLET COMPRESSION[11,13]
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.
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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
Number Description Date
None Tablet press installation, operation and maintenance manual

Table 2: Standard Operating Procedures

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 Table 6: Component Material

Components As-found conditions Component Material
Tablet press motor Manufacturer: Rotor head Mild steel
Model number: Hopper Stainless steel
Serial number: Punches Mild steel
Volts : Dies Mild steel
Amperes :
Phases : Table 7: Lubricants
Cycles :
Where used Type Manufacturer Product contact
hp : (yes/no)
rpm
Motor
clutch Manufacturer : Rotor bead gears
Part number: Punches and dies
Serial number:
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
Table 9: Equipment Control Function Test Results
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. yes
When clutch lever is pushed anticlockwise, the clutch is disengaged
Safety adjusting wheel When safety moving adjusting wheel is turned, the pointer moves yes
operation up and down indicating compression force.
Pressure adjusting When the pressure adjusting wheel is turned, the pressure is yes
wheel operation increased.
Weight adjusting wheel When Weight adjusting wheel is turned, the lower punches are yes
operation lifted.
Hand wheel operation When the hand wheel is turned, the rotor head rotates clockwise. yes
Motor adjusting wheel When the motor adjusting wheel is turned clockwise, the press yes
operation speed increases.
When the motor adjusting wheel is turned anticlockwise, the press
speed decreases.

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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 10: OQ Elements of A Tablet Press

Figure 9: IQ Elements of a Tablet Press

Figure 11: PQ Elements of A Tablet Press

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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
Test Functions[1]
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
Acceptance Criteria[1]
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.
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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. 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. 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

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.
Int. J. Novel Drug Deliv. Tech.| Jul-Sep 2011 | Vol-1 | Issue-3
8.www.validationonline.net
9.http://www.dipharma.com/Tousey_904TC.pdf
10.http://www.labcompliance.com/seminars/audio155/default.a
spx
11.http://www.ksdp.co.in/cts/tender/d_tooling_table_compressi
on_machine.pdf
12.Phil cloud, Pharmaceutical equipment validation-The
ultimate qualification guidebook, Interpharm/CRC press,
Florida; 1998
13.James P.Agalloco, Frederick J.Carleton, Validation of
Pharmaceutical Processes, Third edition, Informa Healthcare,
New York;2007
14.Kenneth W. Sigvardson, Joseph A. Manalo, Robert W. Roller,
F a t i e h S a l e s s , a n d D a v i d Wa s s e r m a n , 2 0 11 :
http://pharmtech.findpharma.com/pharmtech/data/articlestan
dard//pharmtech/502001/4496/article.pdf
15.http://pdfs.findtheneedle.co.uk/8763-BRO-Equipment-
Qualification-e.pdf
16.http://www.laboratoryequipment.com/article-traceable-
equipment-qualification.aspx
17.http://www.hachange.pt/countrysites/action_q/download%3
Bdocument/DOK_ID/14788116/type/pdf/lkz/PT/spkz/pt/TO
KEN/aFlh5FipqcvQh-oJ9ohLbBt5GyY/M/dryWMA

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 Received : 1 Aug 2011
laboratory equipment, the additional validation requirements of Accepted :26 Aug 2011
the computerized systems present many new challenges. Some Published:21 Sep 2011
commercially available software may not completely meet
current requirements. A need exists for greater consistency in the Correspondence to
qualification and maintenance practices for common analytical :Satyabrata Jena
instruments used within the pharmaceutical industry. In today's E-mail: sbjena2007@gmail.com
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
3.http://www.validation-online.net/process-qualification.html
4 . h t t p : / / w w w . a n a l y t i k -
jena.com/files_db/1246610013_1148__22.pdf
5.http://www.chem.agilent.com/Library/service/Public/Review
%20Document_Standard_EQP_LCMS_01.71.pdf
6.http://www.askaboutvalidation.com/forum/showthread.php?1
410-Cleaning-validation-quot-Fuid-bed-dryer-quot
7.http://xlerator-handdryer.com/category/fluid-bed-dryer/

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