a seminar on 1. why to validate? parts of equipment validation who should do equipment...

A

Seminar

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CONTENT:CONTENT:

Why to validate? Parts of Equipment Validation Who should do Equipment Validation? Equipment qualification Typical process flow of solid dosage form Validation of fluid bed dryer Validation of Tray dryer

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WHY TO VALIDATE?WHY TO VALIDATE?

Equipment validation is Vital for • Safety • Fewer interruptions of work • Lower repair costs • Elimination of premature replacement • Less standby equipment • Identification of high maintenance cost • Reduction of variation in results • Greater confidence in the reliability of results

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PARTS OF EQUIPMENT VALIDATIONPARTS OF EQUIPMENT VALIDATION

Equipment

Validation

Equipment

Validation

Installation Qualification (IQ)

Installation Qualification (IQ)

Operational Qualification (OQ) 

Operational Qualification (OQ) 

Performance Qualification (PQ)

Performance Qualification (PQ)

Design Qualification (DQ)

Design Qualification (DQ)

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The user has the ultimate responsibility 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, and 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

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EQUIPMENT QUALIFICATIONEQUIPMENT QUALIFICATION

Equipment qualification / validation includes following things :

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

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Addition of raw material-active excipients

Preble bending-high speed mixer granulator

Granulating - high speed mixer granulator

Drying -fluid bed dryer-tray dryer

Tableting -high speed

rotary

Blending -v-blender

Addition of raw material-lubricant-disintegrants

Sizing -mill/sieve

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TYPICAL VARIABLE OF DRYING PROCESSTYPICAL VARIABLE OF DRYING PROCESS

Control variable

Initial temperature Load sizeDrying temperature programAir flow programDrying timeCooling time

Measured responses

Density Yield Moisture content

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Fixed Variable(monitor)

Response (Test)

Bowl changePorosity of filter bagsBowl sieve

Inlet/exhaust air temperatureProduct temperatureDrying timeAir volumeHumidity of incoming air Humidity of exhaust air

Particle size distributionDensitiesLoss on dryingAssay

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INSTALLATION QUALIFICATION(IQ)INSTALLATION QUALIFICATION(IQ)

Installation Procedure: After checking all the specifications as mentioned

in the selection criteria, service engineer of the manufacturer shall be called for commissioning, if necessary.

Authorized validation team shall carry out installation.

Department Head of production, QA & engineering shall evaluate installation report

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Acceptance Criteria For Installation Qualification: The equipment shall fulfill the selection criteria & its

purpose of Application. Name of the manufacturer & supplier shall be as

mentioned in the Purchase order The manufacturer/supplier shall provide complete

equipment manual along with the equipment All recommended utilities of recommended

capacities are to be provided near the place of installation

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Revalidation Criteria The equipment shall be revalidated if; Location of the equipment is changed. There is change of spare/parts,major maintenance

or breakdown that have a direct effect on the performance of the equipment

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Conclusion: The equipment shall be considered qualified for

installation provided it meets all the parameters mentioned in the acceptance criteria.

After receiving installation report, it shall be evaluated & released for operational qualification, provided installation report is evaluated & the equipment is found meeting all parameters of acceptance criteria

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OPERATIONAL QUALIFICATION (OQ)OPERATIONAL QUALIFICATION (OQ)

Training record Before initiating OQ ensure that SOP for

Cleaning and operation of FBD is available.

• Purpose: To train the qualification team for performing OQ

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Procedure Initiate the actual operation of the FBD to ensure

that machine is operating within specification. Check the OQ parameters against their

specifications. Observe the functioning of all controls available

on control panel Record the observation Perform and attach report of heat distribution

study as per ` Heat distribution study procedure’ 17

Acceptance criteria (Heat Distribution Study:) Temperature difference between all thermocouples

and set temperature should not differ by more than ± 5 °C.

All operating inputs provided on the equipment when tested shall-successfully comply

-meet tolerance limit The equipment should successfully perform when

operated as per SOP18

Critical gauges/indicators provided on the equipment---calibrated

The equipment when operated shall not

- produce abnormal sound

- show any discrepancy in its smooth operation.

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Revalidation Criteria: The equipment shall be revalidated if; Location of the equipment is changed. There is change of spare/ parts, major maintenance

or breakdown that have a direct effect on the performance of the equipment

Critical gauges shall be replaced or corrected At normal revalidation schedule.

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PERFORMANCE QUALIFICATION(PQ)PERFORMANCE QUALIFICATION(PQ) To check Heat Distribution by placing 10

thermocouples in geometric pattern with the FBD Shell and empty Product Container without any load to ensure heat distribution in the drying chamber

Heat distribution study will be performed at 65 ± 5°C for two hour after achieving the temperature on the controlling sensors to ensure proper heat distribution.

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Procedure After completion of OQ initiate the PQ of FBD. The effectiveness of drying will be qualified by

determining reduction of % moisture content in drying process.

3 batches/ lots of any product will be taken for PQ of FBD.

At least 2.0 gm of sample is sampled for % MC check from the top, middle and bottom trays and will be reported

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In case of any deviation inform to department head for necessary action

Document the deviation details Deviation is acceptable or not will be decided

-if yes

-if not

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Acceptance criteria The reduction in moisture content after drying

should be as per the specification in the BMR % RSD of LOD should not be more than 6 % The equipment should produce intended outputs

with respect to quality & quantity consistently

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Revalidation Criteria: The equipment shall be revalidated if; Location of the equipment is changed. There is change of spare/ parts, major

maintenance or breakdown that have a direct effect on the performance of the equipment

At normal revalidation schedule.

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Ensure the cleaning of machine Load the wet mass in the FBD product container Set the process time & outlet temperature and run

the FBD. After completion of drying take out FBD bowl and

collect the sample At least 2.0 gm of sample is sampled for % MC

check from the top, middle and bottom trays and will be reported

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Sampling Procedure: Ware nose mask, hand gloves before sampling. Label the sample bag with details as Product

name, stage, date, time and sign Collect app. 2.0 gms of dried material composite

sample in poly bag as per location shown Record the details of analysis.

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Validation Validation of of Tray dryer Tray dryer

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Fixed Variable(monitor)

Response (Test)

Trays Inlet/exhaust air temperatureProduct temperatureDrying timeAir volumeHumidity of incoming air Humidity of exhaust air

Particle size distributionDensitiesLoss on dryingAssay

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Procedure: Selection criteria shall be defined and based on

specific function to be carried out by the machine & its efficiency.

Requirement of accessories shall be decided & listed out.

Supplier or manufacturer selection

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Purchase Details: The purchase order no. & date shall be checked The accessories & their spare parts if any shall be

checked as per purchase order The delivery period shall be as per purchase order Supplier or manufacturer name & address shall be

checked Any deviation observed should be informed to the

supplier or manufacturer32

Details of the Equipment Equipment name, make & model no. shall be

noted down In-house identification no. shall be allocated Location for installation shall be decided Utilities required shall be listed down

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Installation Procedure: After checking all the specifications as mentioned

in the selection criteria, service engineer of the manufacturer shall be called for commissioning, if necessary.

Authorized validation team shall carry out installation

Department Head of production, QA & engineering shall evaluate installation report

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Acceptance Criteria For IQ Fulfill the selection criteria & its purpose of

Application The equipment shall be as per purchase order Accessories received shall be as per purchase order Should meet pre-selected design parameters Manufacturer/supplier shall provide complete

equipment manual Material of construction shall be as per purchase

order35

Training record Before initiating OQ ensure that SOP for

Cleaning and operation of Tray dryer is available.

Purpose: To train the qualification team for performing OQ

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Procedure Initiate the actual operation of the TD to ensure

that machine is operating within specification. Check the OQ parameters against their

specifications. Observe the functioning of all controls available

on control panel Record the observation

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Acceptance criteria All operating inputs provided on the equipment when

tested shall-successfully comply -meet tolerance limit The equipment should successfully perform when

operated as per SOP Critical gauges/indicators provided on the equipment-

--calibrated The equipment when operated shall not - produce abnormal sound - show any discrepancy in its smooth operation.

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To check Heat Distribution by placing 10 thermocouples in geometric pattern with the TD Shell and empty Product Container without any load to ensure heat distribution in the drying chamber

Heat distribution study will be performed at +45 °C and +105°C for one hour after achieving the temperature on the controlling sensors to ensure proper heat distribution.

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Procedure After completion of OQ initiate the PQ of TD The effectiveness of drying will be qualified by

determining reduction of % moisture content in drying process.

3 batches/ lots of any product will be taken for PQ of TD

At least 2.0 gm of sample is sampled for % MC check from the top, middle and bottom trays and will be reported

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In case of any deviation inform to department head for necessary action

Document the deviation details Deviation is acceptable or not will be decided

-if yes

-if not

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Acceptance criteria Temperature difference between all thermocouples

and set temperature should not differ by more than 5 °C.

The reduction in moisture content after drying should be as per the specification in the BMR

% RSD of LOD should not be more than 6 % The equipment should produce intended outputs

with respect to quality & quantity consistently43

Berry I.R., and Nash R.A., ”Pharmaceutical Process validation” second edition, revised and expanded; Marcel Dekker series; 83-110.

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SEMINAR OPEN FOR DISCUSSION SEMINAR OPEN FOR DISCUSSION

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