“Qualification of Tablet Compression Machine and Dry

Heat Sterilizers”

By
Anjana Sinha
MPH/10036/18
(M.Pharm QA)

Department of Pharmaceutical Sciences & Technology

Birla Institute of Technology, Mesra
Ranchi – 835 215 (Jharkhand) 1
 CONTENTS
Introduction
•Validation
•Calibration
Qualification
Sterilization
Dry Heat Sterilization
Hot Air Oven
•Validation Test Equipment
•Basic Validation Approach
•Qualification Approach
Tablet Compression Machine
•Introduction
•Qualification Approach
Routine Monitor after validation
Conclusion
References 2
INTRODUCTION

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 VALIDATION

• As per USFDA: It is establishing documented evidence which

provides a high degree of assurance that a specific process will
consistently produce a product meeting its pre-determined
specifications and quality attributes.

• Purpose of Validation.?

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 When should be validated ?
• Any Change in established method New method developed for
a particular problem Established method used in different
laboratories, different equipment or different staff Out-of-control
situations within internal quality assurance Demonstration of
equivalence between two methods (e.g. a rapid new test
against a standard method)

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Who should validate?

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• The vendor or the user has the ultimate responsibility for the
accuracy of the analysis results and also for equipment
qualification.
• DQ should always be done by the user.
• While IQ for a small and low cost instrument is usually done by
the user, IQ for large, complex and high cost instruments should
be done by the vendor.
• OQ can be done by either the user or the vendor.
• PQ should always be done by the user because it is very
application specific and the vendor may not be familiar with
these.

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 CALIBRATION

• The process quantitatively defining system responses to known

controlled signal output.

• To determine, check, or rectify the graduation of any instrument

giving quantitative measurements.

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QUALIFICATION

VALIDATION

QUALIFICATION

Qualification is a part of validation

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 QUALIFICATION
• The action of proving that any equipment Works correctly and
leads to the expected results.

• When a validation approach is related to a machine or

equipment which is appropriately designed, located, installed,
operated and maintained to suit their itended purpose.

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 Installation Operational Performance Design
Qualification(IQ) Qualification(OQ) Qualification(PQ) Qualification(DQ)

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12
STAGES OF QUALIFICATION
Design Qualification

Installation Qualification

Operational Qualification

Performance Qualification

Change Control

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 Sterilization
• “The act or process, physical or chemical, that destroys or
eliminates all viable microbes including resistant bacterial
spores from a fluid or a solid.”

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 Gas (Ethylene Other (UV, Steam
Dry Heat Moist Heat Radiation (Gamma oxide, Hydrogen
or electron) & Formaldehyde,
peroxide) Filteration

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 Dry Heat Sterilization
• Dry heat is the most commonly used methods to sterilize
and/or depyrogenate pharmaceutical components
(glasswares) and products. Most often, it is used for
depyrogenation of parenteral containers is performed utilizing
a dry heat oven.
• Dry heat, as the name indicates, utilizes hot air that is either
free from water vapor, and where this moisture plays minimal
or no role in the process of sterilization.
• The process of sterilization within a chamber or hot air tunnel
is a critical process and there is regulatory requirement for
validation of the process.

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 Types of dry heat sterilizers
Commonly employed dry heat sterilizers in pharmaceutical
industry are-
• Forced Convention batch sterilizers.

• Infrared Tunnel sterilizers.

• Forced convention tunnel sterilizers.

• Continuous flame sterilizers microwave

• Laser/Plasma sterilizers.

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 Types of Dry Heat Sterilizers
Commonly utilized dry heat sterilizers in pharmaceutical industry are-

Hot Air Oven The Tunnel System. 18

 HOT AIR OVEN
Higher temperatures and longer exposure times required
• Typical cycles:
• 160°C for 120 minutes

• 170°C for 60 minutes

• 180°C for 30 minutes

• Used for:
• glassware and product containers used in aseptic manufacture, non-
aqueous thermo stable powders and liquids (oils)

• also used for de pyrogenation of glassware.

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Image reference :www.slideshare.net
 Validation Test Equipment
Equipment used for validation testing of oven are listed below:
Resistance temperature detectors

Thermocouples

Data logger

Constant temperature bath

Stopwatch

Voltmeter

Optical tachometer 20
Qualification Approach

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 Basic Validation Approach
Design qualification (DQ):
• The DQ outline the key features of the system designed to address
the user requirement, regulatory compliance and selection rationale
of a particular supplier.

The following are the key considerations for DQ:

• Physical dimensions of the equipment and accessories.

• Suitable operating environment of the instrument

• Health and safety requirement

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Design Qualification
(DQ)

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Image reference : www.slideshare.net
 Installation Qualification
(IQ)
• It is carried out after or concurrently with the installation of the equipment
at the user’s premises.

• The purpose is to provide documentary evidence that the correct

equipment has been received and installed as per plan and protocol.

• IQ documents should be reviewed and approved by designated

responsible individuals.

• It includes details of-

• Structural- Check dimensions, presence of seal
• Filters- Proper identification,type,size,air capacity, flow rate

Contd.
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• Electricals- Proper identification, safety cutoff

• HVAC- System provides the temperature and pressure differential

required.

• Air supply- Identify source, duct size.

• Air or natural gas- Check that the source and type of supply are
consistent with the manufacturer’s recommendations.

• Heaters- Record the manufacturer's model no., the no. of heating

elements.

• Blowers- Check for use of correct fan belt & that is in good condition.
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 Operational Qualification
(OQ)
• It is documented verification that the system or subsystem
performs as intended throughout all specified operating range

• The OQ document should be reviewed and signed by the

required department representatives.

• The components of system must satisfy the operating ranges

as determined by the purchase order specifications.

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 Each of the following process components must be identified & the
operating performance & range determined.
• Cycle timer - The accuracy of timer must be determined, so that assurance is
provided for cycle time.

• Door interlocks - If a unit is equipped with double doors, the interlocks must
operate such that the door leading to the aseptic area cannot be opened if the door
to the non-aseptic area is opened.

• Heaters - All of the heating elements must be functional.

• Blowers - The air velocity consistent and motor speed of blowers should be noted
in the OQ records.
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• Cooling Coils- If coils are present, the type and size of the coils and temperature of
the cooling medium at the inlet and outlet of the coils should be recorded.

• Chamber leaks- The perimeter of the doors for batch sterilizers should be checked
for air leakage while operating.

• Particulates counts- Particulate count should be checked within the containers

before and after sterilization to quantitate the particle load contributed to the
product by sterilization process.

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 Performance Qualification
(PQ)
• Verifies that the equipment performs according to design
specifications and user defined requirements in a reliable &
reproducible manner under normal production conditions
• Physical -
• Heat penetration studies on empty chamber
• Heat distribution study on loaded chamber
• Heat penetration study on loaded chamber
• • Microbiological-
• Bio-challenge/ Pyro -challenge studies

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 Physical
• Heat Penetration Studies On
Empty Chamber
To identify heat distribution patterns
including slowest heating points
 Multiple temperature sensing
devices should be
used(Thermocouples)
Temperature profile locate hot/cold
areas in the sterilizer by mapping
temperature at various location.
• Heat Distribution Study on
Loaded Chamber
. Multiple thermocouples throughout
chamber to determine effect of load
configuration on temperature
distribution.
Temperature distribution for all
loads using all container sizes used
in production should be tested.
Repeat runs should be performed
to check variability.
Temperature profile for each
chamber load configuration should
be documented
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 Cont..
• Heat Penetration Study on • Bio-Challenge/ Pyro-Challenge
Loaded Chamber Studies
 Designed to determine the  The challenge should
location of the slowest heating demonstrate the lethality delivered
point within a oven at various by the cycle with either
locations. microorganisms or endotoxins
 Each size & type of material Resistant bacterial spores are
should be tested by penetration available primarily in the form of
studies. spore strips andSpore suspension.
Hot areas in the load are more
important for heat labile items.
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Tablet Compression Machine

Image reference:
http://www.pharmainfo.net/equipment-validationarticles/laboratory-equipment-qualification 33
Introduction Of Compression Machine
• Compression is a critical step in the production of a tablet
dosage form. The materials being compressed will need to
have adequate flow and compression properties.

• Factors to consider during compression are as follows:

i)Tooling
ii)Compression speed

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Qualification Approach

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 Installation Qualification
(IQ)
• Verity approved purchase order.
• Verity invoice Check manufacturer and supplier.
• Verity 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 instructions provide in the manual.

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Objective of IQ:
• To Check all the critical contact parts which directly affect quality
of the product either visually or by kit.
• To review proper installation as per checklist.
• To measure the dimension wherever possible

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 Installation Qualification check list :
• Compare the all specification and write
the observation Machine height - Measure
with measuring tape
• Overall Dimension - Measure with
measuring tape RPM of turret (max. &
min.) -
• Check by tachometer Hopper
Conventional hopper - by visually check
MOC (Material of construction) –
• Kit Height - Measure with measuring tape
• No. of station - Visually count no. of holes
on turret
• Type of tooling - Using Venire caliper
check the die hole diameter
• Turret MOC – by visual check
• Circumference – Measure with measuring
tape
• Distance between two dies - Using Venire
caliper
• Feeder - by visual check Main electrical
motor
• HP – Visually check by reading plate
affixed on motor
• RPM - Visually check by reading plate
affixed on motor or Direction of motor (anti
clockwise) -by visual check
• Thickness controller
• Weight controller
• Emergency switch
• Dust Extraction and exhaust System Main
drive Available ON Indicator
• By visual Potentiometer check Selector
switch Emergency OFF button
• Lubrication Oil pressure gauge Selector
switch for Auto/ Manual
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 Operation Qualification
(OQ)
• 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 operation
manual to verify the operation control.
• Verify that all switches and push buttons are functioning properly.
• Establish procedures for operation, maintenance and calibration
• Establish training program for relevant staff.
• Run one pilot batch for each product

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Objective of OQ :
• To operate machine as per proposed procedure given in manual and
record.

• To challenge the operating parameters of machine and record.

• To challenge the safety operation and record.

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• Operational qualification check list :
1)Compare the all specification and write the observation
Main Switch – Check visually by operating the main switch
of the machine .
2)Start push button – (illuminated Green switch)By pressing
start button the Green switch glows and the main drive
motor should start.
3)Stop push button - (illuminated red switch) By pressing
stop button the red switch glows and the main drive motor
should stop.

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4) Turret RPM challenge test – set in digital table counter by rotating
knob Check by tachometer Rotation direction ( clock wise) by visual
check
5)Emergency switch (Machine should be stop)
6) Selector/ isolator switch (Machine start/stop) By
7) Tablet thickness Visually & Hardness controls check By turning
the swing lever to right (anticlockwise) thickness increased/
hardness decrease vise versa
8 ) Tablet weight controls Dozer and wedge is moved clockwise
Decrease / increase / Anti clockwise weight

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 Performance Qualification
(PQ)

• Evaluation of compressing capabilities and Tablet

characteristics. The compressing capabilities and table
characteristics (i.e. content uniformity , thickness , hardness ,
friability , weight variation and disintegration time) should be
investigated .

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Objective of PQ:

• First three batches/product of bilary and single layer product to

be compressed on given compression machine.

• All the critical physical parameters of the product will be checked

during performance qualification.

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• Performance qualification check list :

• Compare the all specification and write the observation of all

3 batches
• Product name
• Average weight of 20 Batch No Tablet Batch size
• Individual Weight Product description variation Machine
RPM
• Thickness (mm)
• Punch detail Hardness ( Kg/cm2 )
• Punch diameter Punch Shape Upper punch/ Lower punch
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 Routine Monitor After Validation
• The unit must be monitored so that it remains in a state of
control
• This is achieved by the use of various programs
including-

Sanitization:
• It should detailed the cleaning methods used for the equipment,
the SOPs covering each method, and the cleaning materials
utilized.

• Cleaning materials should be nontoxic and leave no residues.

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Preventive maintenance-
• It provides a schedule by which the equipment is maintained.
• A proper PM program will help to prevent breakdown during production.

Change control-
• Changes to the equipment that might compromise the validation must be
brought to the attention of the group or individuals in charge of the change
control program.

Revalidation-
• It may be required after changes or repairs are made on the unit or an a
predetermined periodic interval.

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Documentation

• All validation information should be easily identified and kept in a

permanent central file, where it can be readily retrieved.

• The validation file should include the following information:

Qualifications

• This includes all steps performed in the certification of the

equipment .
• All original data, results and conclusion must be contained in this
file.
• All reports should be dated,signed,and approved by the
responsible individuals. 48
Process Qualification Protocol:
• The protocol is located in this file.

Raw Data:
• All original data, results, calculation and conclusions must be retained for
empty- and loaded chamber and biochallenge studies

 Process Qualification Report:

• It is the formal document available for regulatory review

 Routine Monitoring:
• All change-control information and postvalidation mechanical changes are
recorded along with any revalidation work
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 Conclusion
• Equipment is one of the basic component of pharma processing and
therefore equipment validation is an important aspect.

• Validation of Hot Air Oven/Tablet Compression machine is the part of

comprehensive validation program within a company.

• The validation of Hot Air Oven/Tablet Compression machine prove its

repeatability.

• Equipment validation give the surety that equipment having good

qualification like design, operation, installation and performance
qualification which have predetermined.

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 References
1. Laurie BC, Gayle DH, Dry Heat Sterilization and Depyrogenation Validation and
Monitoring, In:, James AF, Carleton J, Editors. Validation Of Pharmaceutical
Process, informa healthcare; P. 223-239.
2. Potdar AM. Pharmaceutical Quality Assurance,1st ed. Published by Nirali
Prakashan; 2006.P. 8.13-8.20.
3. Syed Imtiaz Haider. Pharmaceutical Master Validation Plan. The Ultimate Guide to
FDA,GMP and GLP Compliance. informa healthcare;2010. P.138-139.
4. https://biologicalindicators.mesalabs.com/2015/12/14/validation-of-dry-heat-
sterilizationprocesses
5. https://www.pharmatutor.org/articles/validation-dry-heat-sterilization-methods.
6. http://www.mackpharmatech.com/doc.htm
7. http://www.ehow.com/list_6809815_equipment

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