Qualification of manufacturing equipment.pdf

It is very helpful ful document for students studying in m pharm 2nd semester. It is well made for semester examination purpose and to understand the requirements as per regulatory guidelines. The content will be helpful for you all .

1. QUALIFICATION OF MANUFACTURING
EQUIPMENTS
SUBMITTED BY: ASHA DHAKAL
QUALITY ASSURANCE (2
ND
SEMESTER)
35/MQA/DIPSAR/23
PHARMACEUTICAL VALIDATION (202T)
DELHI INSTITUTE OF PHARMACEUTICAL SCIENCES AND RESEARCH

2. TABLE OF CONTENT
•QUALIFICATION AND ITS OBJECTIVE
•DRY HEAT STERILIZATION/ TUNNELS
•AUTOCLAVES
•CAPSULE FILLING MACHINES
•REFERENCES
Asha Dhakal DIPSAR

3. QUALIFICATION AND ITS OBJECTIVE
The process of testing equipment, instruments, services, utilities and related systems. A collection
of actions carried out or completed to verify and confirm that the equipment and utilities are fit
for their intended purpose and perform correctly is qualification.
OBJECTIVE
Easy maintenance of equipment and safety
To prove overall production reliability and productivity
Control product quality
Lower the repair cost
Identification of high maintenance cost
Asha Dhakal DIPSAR

4. •It comes under the thermal physical method of sterilization
•It is commonly used to sterilise and depyrogenate pharmaceutical components, glassware and
products. The depyrogenation of the parenteral container is performed utilizing a dry heat oven.
•Resistant spores are killed by exposing them at high temperatures for a long period.
Commonly used dry heat sterilization
DRY HEAT STERILIZATION/TUNNELS
Conventional Hot Air
Oven
Tunnel sterilizer
Asha Dhakal DIPSAR

5. TYPES OF DRY HEAT STERILIZATION
•High temperature and longer exposure time required
•Typical cycle of hot air oven is 160⁰C for 120 minutes, 170⁰C for 60 minutes, 180⁰C for 30 minutes.
•The hot air oven is the equipment which is utilized to provide the dry heat medium and it must be validated to
ensure that the system can provide sterile and depyrogenatedcomponents, on a reproducible basis
(The major difference between the hot air oven and tunnel system, as far as validation is concerned is the belt
and line of speed variable with the tunnel system)
HOT AIR OVEN TUNNEL SYSTEM
Asha Dhakal DIPSAR

6. The DQ outlines the key features of the system designed to address the user requirements, regulatory compliance and
selection rationaleof a particular supplier. The following are the key considerations:
Physical dimension of the equipment and accessorise
Suitable operating environment of instrument
Health and safety management
The DQ includes:
Facility layout
Decision of batch and continuous process
Utility requirements and specifications
Pressure differential requirement
Required capacity of the sterilizer
Type of material to be sterilized
DESIGN QUALIFICATION
Asha Dhakal DIPSAR

7. •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 thedetails included are :
Structure-check dimensions, presence of seal
Filters-proper identification, type, size, air capacity, flow rate
Electrical-proper identification, safety cutoff
HVAC-the system provides the temperature and pressure differential required
Air and natural gas -check the source and type of supply are consistent with the manufacturer’s
recommendation
Blowers-check the use of the correct fan belt & that is in good condition
Heaters-Record the manufacturer model no., the no. of heat elements
INSTALLATION QUALIFICATION
Asha Dhakal DIPSAR

8. •It is the documented verification that the system or subsystem performs as intended throughout
all specified operating ranges.
•the OQ document should be reviewed and signed by the required department representative.
•the component of the system must satisfy the operating ranges as determined by the purchase
order specifications.
Temperature monitors-the temperature recorder, sensor and controller must be calibrated
before the unit can be operated reliably
Cycle timer–the accuracy 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 it is preferable to have them monitored
continuously with ammeters so that burned out elements can be immediately detected
OPERATIONAL QUALIFICATION
Asha Dhakal DIPSAR

9. •Cooling coils-to enable a faster cool-down cycle, the air is often circulated across coolant
coils
•Belts –the belt speed is a critical operating parameter in continuous hot air tunnels.
Recorders for charting the belt speed are recommended for units with adjustable speed
settings
•Particulate counts:-it should be checked before and after sterilization
•Chamber leaks –The parameters of the doors for batch sterilizers should be checked for
air leakage while operating.
OPERATIONAL QUALIFICATION CONT.
Asha Dhakal DIPSAR

10. PERFORMANCE QUALIFICATION OF HOT AIR OVEN
(1)Air balance determination: in an empty oven, data are obtained on the flow rates of both intake &
exhaust air. Air should be balanced so that positive pressure is exerted on the nonsterile side when the
door is opened
(2)Heat distribution of an empty chamber: The thermocouple should be situated according to a specific
predetermined pattern
(3)Heat–penetration studies: These studies should be designed to determine the location of the slowest
heating point within a commodity at various locations of a test load in the sterilizer. Thermocouples are
placed in the commodities located in that are likely to present the greatest resistance to reaching the
desired temperature
(4)Mechanical repeatability: during all these studies, mechanical repeatability in terms of air velocity,
temperature consistency, reliability & sensitivity of the oven and instrument controls must be verified
Asha Dhakal DIPSAR

11. PERFORMANCE QUALIFICATION OF TUNNEL
STERILIZER
(1) Air balance determination: In this study, items being sterilized are moving and exposed to different air systems (e.g.,
heating zone & cooling zone)
Air flow must be balanced to provide a gradual decrease in air temperature as items move along the conveyor
(2) Heat distribution of an empty chamber: the thermocouple used in tunnel sterilizer validation must be sufficiently
durable to withstand the extremely high temperature (2300⁰C) in the heating zone area of the tunnel
Heat distribution studies should determine where the cold spots are located as a function of the width of the belt & height of
the tunnel chamber
(3) Heat–penetration studies: These studies should be designed to determine the cool spot of the entire load.
3 to 5 replicate runs for each commodity size & every loading configuration should be done using 10 to 20 thermocouples
distributed throughout the load
Careful analysis of the temperature data after each run will be valuable in the determination of cool spot
(4) Mechanical repeatability: during all these studies, mechanical repeatability in the same manner as batch ovens
Air velocity, air particulate, temperature consistency & reliability of all the tunnel controls (heat zone temperature, belt
speed) must be proved during physical validation studies.
Asha Dhakal DIPSAR

12. •The autoclave works on the principle of moist heat sterilization, where steam under pressure is used to sterilize the material
present inside the chamber.
•When water is heated in a closed container, saturated steam is produced under pressure.
•Hot saturated steam is an efficient means of destroying organisms since it penetrates rapidly and gives up its latent as it
condenses on the cooler objects.
•It is used to sterilize medical devices, surgical instruments, supplies and equipment utilize in direct patient care and surgery.
QUALIFICATION OF AUTOCLAVE
Asha Dhakal DIPSAR

13. •Design qualification (DQ) defines the functional and operational specification of the instrument and details for the
conscious decision in the selection of the supplier.
•The steps that should be considered for inclusion in the DQ of the autoclave:
1)Description of analysis problem
2)Description of the intended use of the equipment
3)Description of the intended environment
4)Instrument test
5)Preliminary selection of the suppliers
6)Final selection of the equipment
7)Final selection of the supplier and equipment
•The first qualification stage of an autoclave starts as soon as you formulate and document your requirements for the
devices to be purchased.
DESIGN QUALIFICATION
Asha Dhakal DIPSAR

14. •The IQ procedure is used to demonstrate that the autoclave as installed meets all specifications, is installed
properly and that the supporting programme needed for ongoing operation (EX:-SOPs) is in place
•The IQ involves following a checklist-
Mechanical equipment specifications: chamber, valves, traps, filters, regulators, vacuum pump, heat
exchanger, condenser etc.
Control and instrumentation specification: printer recorder, control valves, pressure and temperature,
transmitter, resistance temperature device, switches, level sensors, interlock etc.
Drawing verification
Construction materials
Change part
instrument calibration
INSTALLATION QUALIFICATION
Asha Dhakal DIPSAR

15. •Installation qualification (IQ) conducted to prove that equipment/system has been installed as per user and
manufacturer recommendation and verifying that all required utilities have provided safe operation of
equipment/ system.
Utility specification
Drawing specification (electrical, mechanical)
Construction material in product contact
Operating and maintaining manual
INSTALLATION QUALIFICATION CONT.
Asha Dhakal DIPSAR

16. •Operational qualification (OQ) is the process of demonstrating that an instrument will function
according to its operational specification in the selected environment. “The proper operation of
equipment is verified by performing the test functions specified in the protocol”. A conclusion is
drawn regarding the operation of equipment after the functions are checked and all data has been
analyzed.
•The OQ process is intended to demonstrate that the components are operating properly and ready for
performance or load testing. Operational qualification shall be done “without load”
•OQ testing typically includes the following tests:
Empty chamber temperature mapping.
Simulated load chamber temperature mapping and if required verification of sterilization efficacy
using a biological indicator.
Alarm condition and expected results.
OPERATIONAL QUALIFICATION
Asha Dhakal DIPSAR

17. •Operational qualification of autoclave involves points to be checked:
Check the alarms
Temperature too high or too low
Pressure too high or too low
Time limits of process steps
Utility supply
Cable break of sensors
Filter sterilization
Saturated steam check
leak?/steam penetration test
Empty chamber test
OPERATIONAL QUALIFICATION CONT.
Asha Dhakal DIPSAR

18. •Performance Qualification (PQ) is the process of demonstrating that an instrument consistently performs according to
specifications appropriate for its routine use. PQ should always be performed under conditions that are similar to routine
sample analysis.
•PQ is documented evidence to prove that equipment/system is performing under specified conditions. It involves taking trial
under “loaded conditions”
•The test includes in PQ:
Heat distribution studies: It includes 2 phases
Heat distribution in an empty autoclave chamber
Heat distribution in a loaded autoclave chamber
•Heat-distribution studies may employ thermocouple at the cool spot in the chamber
•The principle is to found the cool spot & the mean chamber temperature should not greater than 2.5⁰C
Loaded chamber steam penetration test:
•it involves the determination of load items difficult to sterilize and worst-case location. While performing the test load
configuration is taken into consideration.
PERFORMANCE QUALIFICATION
Asha Dhakal DIPSAR

19. CAPSULE FILLING MACHINE
Process flow, variables and responses: capsule
Asha Dhakal DIPSAR
Qualifying the machine, the company ensures that every capsule has the correct
amount of medicine, making the drug safe and effective for patients.

20. TYPES OF CAPSULE FILLING MACHINES
Rotary die soft gelatin capsule filling Hand operating capsule filling machine
Compression filling method Semi solid dosage form filling system
Asha Dhakal DIPSAR

21. CONTROL PARAMETERS
FOR HARD GELATINE CAPSULE FILLING
FOR SOFT GELATINE CAPSULE FILLING
Asha Dhakal DIPSAR

22. •The IQ will confirm details :
The engineering specification
Equipment purchase order
CGMP guideline requirements, verify that the equipment has been installed as specified by the
vendor
•Purchase details:
Purchase order no. The date shall be checked
The accessories and their spare parts if any shall be checked as per the purchase order
the delivery period shall be as per the purchase order
Supplier and manufacturer names shall be checked
Any deviation must be informed to the supplier or manufacturer
INSTALLATION QUALIFICATION
Asha Dhakal DIPSAR

23. •Details of the Equipment:
Equipment name, make model no. shall be recorded
In-house identification no. shall be recorded Location for installation shall be checked Utilities required shall be listed down
A detailed specification must be written that highlights those parts of the machine that are in product contact
Where stirring devices or augers are used to ensure homogeneity and improve flow the specification of these parts must be
checked
•Acceptance Criteria For IQ
Fulfil the selection criteria & the purpose of the Application
The equipment shall be as per the purchase order
Accessories received shall be as per the purchase order
Should meet pre-selected design parameters
Manufacturer/supplier shall provide complete equipment manual
Material of construction shall be as per purpose
INSTALLATION QUALIFICATION CONT.
Asha Dhakal DIPSAR

24. Before initiating OQ ensure that SOP for Operation and Cleaning of the Capsule Filling Machine is available.
Purpose: To train the qualification team for performing OQ
Procedure:
Check all the dynamic attributes of the capsule filler conform to the required specifications
Initiate the actual operation of the equipment to ensure that the machine is operated within the desired rate of output.
The operation of indicators, controls and alarms is verified
Oil leaks that could contaminate the process are observed
Acceptance criteria:
All operating inputs provided on the equipment when tested successfully comply-meet tolerance limit
The equipment should successfully perform when operated as per SOP
Critical alarm/indicators provided on the equipment---calibrated
The equipment when operated shall not produce abnormal sound and show any discrepancy in its smooth operation.
OPERATIONAL QUALIFICATION
Asha Dhakal DIPSAR

25. •PQ activities demonstrate and document that the equipment can perform its intended functions within
the variable process limits for a specific product
•Acceptance criteria are developed according to the regulatory requirements and production parameters
•To ensure that the quality and purity of the product is maintained
•The PQ process may also include several challenges to the system challenging the operating limits.
•The PQs require replicate testing; triplicate testing is the generally accepted minimum.
•The PQ will also test the extremes of the operation, or the peak load conditions, but it does not include
testing for failure
PERFORMANCE QUALIFICATION
Asha Dhakal DIPSAR

26. •Procedure
The accuracy and precision of placebo powder fill will be evaluated for each capsule size that
will be used in normal production
Record the number of damaged capsules
Capsules from throughout the lot/different batches should be tested for weight uniformity
Capsules from throughout the lot/different batches should be tested for blend content
uniformity
Production speed i.ecapsule per minute should be evaluated
PERFORMANCE QUALIFICATION CONT.
Asha Dhakal DIPSAR

27. •The earlier steps (IQ, OQ, PQ) focus on ensuring the machine works properly after being
built, installed, and ready to run. Design Qualification happens beforethe machine is
purchased or built. It ensures that the machine’s design is appropriate for the intended use.
Asha Dhakal DIPSAR
WHY IS DQ NOT EXPLAINED IN THE CAPSULE -
FILLING MACHINE?

28. REFERENCE
•https://www.slideshare.net/slideshow/qualification-of-tablet-compression-machine-capsule-
filling-machine/226418800
•Shinde, S.J., Jain, P.S. and Kale, N.K., 2013. Critical review on qualification of sterilization
equipment in aseptic processing.Department of Quality Assurance and Pharmaceutical
Chemistry, RC Patel Institute of Pharmaceutical Education and Research, Shirpur, Dhule
(MS), India.
•https://www.slideserve.com/fearghus/validation-of-capsule-filling
Asha Dhakal DIPSAR

29. THANK YOU
Asha Dhakal DIPSAR
.