VALIDATION OF FLUIDIZED BED DRYER

 Introduction
 Fluidized bed dryer has extensive usage in pharmaceutical industries
in order to reduce the moisture content pharmaceutical granules and
powders
 This machine has excellent gas particle constant which enables it to
produce a high rate of moisture removal the results in high mass and
heat transfer rates
  The equipment works on a principle of fluidization of the feed
materials

 In fluidization process, hot air is introduced at high pressure through

a perforated bed of moist solid particulate.

 The wet solids are lifted from the bottom and suspended in a stream
of air (fluidized state).

 Heat transfer is accomplished by direct contact between the wet

solid and hot gases.

 The vaporized liquid is carried away by the drying gasses. Sometimes

to save energy, the exit gas is partially recycled.

 User requirement specification (URS)

User requirement specifications are the basic document that covers all the
needs of the manufacturing department. URS of fluidized bed processor was
prepared by a coordinated approach among production, quality assurance, and
engineering department, considering all the GMP requirements the machine
has to fulfil.

 Qualification protocol
The qualification protocol is the center of gravity of validation documentation
process. The protocol is industry tool used to document the qualification
 process but it can take any form. Major elements of qualification protocol are
given in Fig. 1 and Fig. 2 below
Protocol Package
contents
Certification
Page
Final
report
Protoc
ol

Installation qualification Operational qualification

Performance qualification

Attachme
nts
Fig.1. Qualification Protocol Documentation

Qualification Protocol

Installation qualification Operational qualification Performance qualification

Equipment description Calibration requirement

Equipment identification Equipment control functions
Utility requirements Equipment operation
Component materials Lubricants
Safety features
Fig.2. Qualification Protocol Elements Qualification

 Machine description
Complete machine can be divided in following subsections:
  Inlet air system: It consists of compressed air supply, filtering and
regulating unit, air flow meter, heating chamber consisting of heating
element, process air control valve.
 Machine tower: It consists of lower plenum where the bottom spray gun
fixing port is provided, product container to hold powders, expansion
chamber with spray port, acrylic windows to view the process, filter
housing to view the process and filter housing to fix product retaining
cartridge filter.
 Spray system: Consists of peristaltic spray pump and spray gun with
atomizing air connection.
 Electrical system: consists of electrical panel with contactors, terminals,
SMPs and logic controls.
 Pneumatic system: consists of air reservoirs, pressure regulator and
gauges.
 Indication and control elements: consists of temperature control/
indicator, operating switches, pressure regulators and indicators.

 Qualification
An equipment validation program can be described in four sequential phases:
Prequalification, Qualification, Process qualification and Process validation.
Prequalification includes vendor specification, design and operation checkout.
Qualification includes installation and operational check out including design
qualification, installation qualification, operational qualification, performance
qualification and maintenance qualification.
 DQ
 Design qualification defines the functional and operational
specifications of the instrument
 DQ qualification is done by comparing observation with users
requirements

Sr. Specification Demanded Observation Complie

No s
.
1 Output Capacity of 100 -120kg 100-120kg yes
 equipment
2 Material used for S.S - 316 S.S. - 316
product container
3 Capacity of heater 2 k.w. s.s. made 2 k.w. s.s. made
4 Total volume of 567 liters 567 liters
product container in
liters
5 Rubber gasket D Type of silicon D type of silicon
material
6 Blower Aluminium Aluminium
7 Heating media Steam cum Steam cum
electric electric
8 Material used for S.S. Steel S.S.Steel
blower

 IQ
 In installation qualification, the three have to be validated,
 They are 1. Mechanical 2. Electrical and 3.General

1. Mechanical

S. Name of the parameter Acceptance Compliance

No criteria
1 Moving parts and pinch points Yes
adequately guarded.
2 Machine suitably embedded Yes
(grounded).
3 All service lines properly connected Yes
4 Change parts correctly fittings Yes

2. Electrical

S. Name of the parameter Acceptance Compliance

N criteria
o
1 All electrical wiring connected Yes
within machine body
2 Electrical earthing proper Yes
3 Safety cut outs/interlocks working Yes
4 Limit switches connected Yes

3. General

S. Name of the parameter Acceptance Compliance

No criteria
1 Adequate working space around the Yes
machine
2 Lightning arrangements adequate Yes
3 Ventilation adequate No
4 Preventive maintenance procedure Yes
and schedule prepared

 OQ

S. Name of the parameter Observation Compliance

N
o
1 Machine when puts on starts Yes
working.
a. Noted the sequence to put on the
machine
2 Machine when puts off stops Yes
working
b. Noted the sequence to put off
the machine
3 Emergency stop switch puts off Yes
maintenance even during mid
sequence

Machine “ON”

S. Name of the parameter Observation Compliance

No
1 All signal lamps/indicators lit Yes
2 Directions of run correct Yes
3 Sequence of operation proper Yes
4 Conveyer/vee belts movement Yes
smooth
5 R.P.M. of motor, gearbox and Yes
other parts proper
6 All measuring instruments are
working and calibrated. Yes
 Thermometer Yes
 Pressure gauge Yes
 Electrical motors Yes
 Temperature recorders
7 Noise level of running machine as Yes
per specifications
8 Vibration of machine within Yes
tolerance

Machine “Off”

S. Name of the parameter Observation Compliance

No
1 All signal lamp/indicators off Yes
2 No jamming of product when Yes
machine is put off in mid sequence
3 Inching switch in working order Yes

 PQ
Performance qualification is done using empty load and with
load to check the performance of the machine. It is done as
follows.

1. Timer calibration – to ensure timer performs as per

specifications
2. Shaker validation – to ensure shaker is functioning as per set
specifications.
 3. Empty load validation to check the performance of heat
bank 1,2,3 & 1,2 & 3 at different temperatures.
4. Empty load validation to check the performance of steam at
different temperatures.
5. Empty load validation to check the performance of heat
bank 1,2,3 & 1,2 & 3 at varying time interval.
6. Empty load validation to check the performance of steam at
varying time interval.
7. Load validation to check the reduction in moisture content
of the product at different temperatures (45 0C, 500C, & 600C)
using both steam and heat banks.
8. The analysis is done by Karl Fisher method

K.F. Formula =

Titre value × K. F. Factor

Weight of substance taken × 10

9. Load validation to check the particle size during drying using both
steam and heat banks at different temperature (450C, 500C, & 600C).

 Maintenance qualification (MQ)

Maintenance qualification is used to describe and document regular
maintenance and repairs. As a result, this helps ensure that the equipment can
be continuously operated to avoid downtime. Maintenance qualification
covers all necessary measures entailing cleaning, maintenance and repair. This
work is documented in a service logbook.
 Performance test
 Test run (Top spray) Granulation Test run of the equipment for
granulation was done for both minimum and maximum load of the
equipment. Equipment was run as per the Standard Operating
Procedure(SOP) and monitoring all the parameters of coating like; inlet
air temperature, bed temperature, spray rate/gun, no. of gun, process
 air flow, atomizing air pressure, peristaltic pump speed and purging time
were recorded. After completion of the process samples were
withdrawn (as per sampling plan) and were analysed for % loss on
drying, bulk density, tap density, particle size distribution and assay. All
the samples analysed complies with the requirements and are with in
acceptable limits.

Observation
S. Granulation Requiremen
No parameter t Minimum Maximum
. load (250 ml) load (750 ml)
1 Peristaltic 1-25 rpm
pump speed
2 Atomizing air 1-3 bar
pressure
3 Process air 0.5 -1.5 bar
flow pressure
4 Number of 01
guns
5 Spray rate per Record
gun
6 Inlet air temp. 45–5 C
7 Bed temp. 35–5 C

8 Purging time 1-5 second

Table : Process monitoring (Top spray) Granulation

S. Parameter For minimum load For maximum load

No.
1 Mean assay
2 %RSD
3 % LOD
4 Bulk density
5 Tap density
6 Sieve analysis +40# +40#
+60# +60#
 ˂ 100# ˂ 100#
+ 100# + 100#
Table : Task reports (Top spray) Granulation
 Test run (Bottom Spray) Wurster coating
Test run of the equipment for wurster coating (Bottom spray) was done for
both minimum and maximum load of the equipment using non peril seeds.
Equipment was run as per the SOP and monitoring all the parameters of
coating like; inlet air temperature, bed temperature, spray rate/gun, no. Of
gun, process air flow, atomizing air pressure, peristaltic pump speed and
purging time. After completion of the process samples were withdrawn (as per
sampling plan) and were analysed for % loss on drying, % yield, weight build up
and assay. All the samples analysed complies with the requirements and are
with in acceptable limits.

Observation
S. Coating Requirement Minimum Maximum
No parameter load (250 load (750
. ml) ml)
1 Peristaltic 1-25 rpm
pump speed
2 Atomizing air 1-3 bar
pressure
3 Process air 0.5 -1.5 bar
flow pressure
4 Number of 01
guns
5 Spray rate Record
per gun
6 Inlet air 45–5 C
temp.
7 Bed temp. 35–5 C
8 Purging time 5-60 second
Table : Process monitoring (Bottom spray) Wurster coating

S. Parameter For For

No minimum maximum
. load load
 1 Mean assay
2 %RSD
3 % LOD
4 % yield
5 %Weight
build up
Table : Task reports (Bottom Spray) Wurster coating