A Seminar on VALIDATION OF FLUID BED AND

A Seminar on VALIDATION OF FLUID BED AND TRAY DRYER 1

CONTENT: q Why to validate? q Parts of Equipment Validation q Who should do Equipment Validation? q Equipment qualification q Typical process flow of solid dosage form q Validation of fluid bed dryer q Validation of Tray dryer 2

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 3

PARTS OF EQUIPMENT VALIDATION Design Qualification (DQ) Performance Qualification (PQ) Equipment Validation Installation Qualification (IQ) Operational Qualification (OQ) 4

WHO SHOULD DO EQUIPMENT VALIDATION? THE VENDOR OR THE USER? q The user has the ultimate responsibility for equipment qualification. q DQ should always be done by the user. q 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. q OQ can be done by either the user or the vendor. q PQ should always be done by the user 5

EQUIPMENT QUALIFICATION q Equipment qualification / validation includes following things : Design qualification (DQ) Installation qualification (IQ) Operational qualification (OQ) Performance qualification (PQ) 6

TYPICAL PROCESS FLOW OF SOLID DOSAGE FORM Addition of raw material -active excipients Tableting -high speed rotary Preble bending -high speed mixer granulator Blending -v-blender Granulating - high speed mixer granulator Addition of raw material -lubricant -disintegrants Drying -fluid bed dryer -tray dryer Sizing -mill/sieve 7

TYPICAL VARIABLE OF DRYING PROCESS Control variable Initial temperature üLoad size üDrying temperature program üAir flow program üDrying time üCooling time ü Measured responses Density üYield üMoisture content ü 8

VALIDATION OF FLUID BED DRYER 9

FLUID BED DRYER 10

FBD CONTROL PARAMETERS Fixed Variable (monitor) Response (Test) ØBowl change ØPorosity of filter bags ØBowl sieve ØInlet/exhaust air temperature ØProduct temperature ØDrying time ØAir volume ØHumidity of incoming air ØHumidity of exhaust air ØParticle size distribution ØDensities ØLoss on drying ØAssay 11

INSTALLATION QUALIFICATION(IQ) q 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. ü Authorized validation team shall carry out installation. ü Department Head of production, QA & engineering shall evaluate installation report ü 12

Conti… q ü ü 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 13

Conti… q Revalidation Criteria v The equipment shall be revalidated if; ü Location of the equipment is changed. ü There is change of spare/parts, major maintenance or breakdown that have a direct effect on the performance of the equipment 14

Conti… q Conclusion: The equipment shall be considered qualified for installation provided it meets all the parameters mentioned in the acceptance criteria. ü 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 ü 15

OPERATIONAL QUALIFICATION (OQ) q Training record ü Before initiating OQ ensure that SOP for Cleaning and operation of FBD is available. • Purpose: To train the qualification team for performing OQ 16

Conti… q Procedure Initiate the actual operation of the FBD to ensure that machine is operating within specification. ü Check the OQ parameters against their specifications. ü Observe the functioning of all controls available on control panel ü Record the observation ü Perform and attach report of heat distribution study as per ` Heat distribution study procedure’ ü 17

Conti… q Acceptance criteria (Heat Distribution Study: ) ü Temperature difference between all thermocouples and set temperature should not differ by more than ± 5 °C. ü All operating inputs provided on the equipment when tested shall-successfully comply -meet tolerance limit ü The equipment should successfully perform when operated as per SOP 18

Conti… Critical gauges/indicators provided on the equipment---calibrated ü The equipment when operated shall not - produce abnormal sound - show any discrepancy in its smooth operation. ü 19

Conti… q Revalidation Criteria: v The equipment shall be revalidated if; ü Location of the equipment is changed. ü There is change of spare/ parts, major maintenance or breakdown that have a direct effect on the performance of the equipment ü Critical gauges shall be replaced or corrected ü At normal revalidation schedule. 20

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 ü 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. ü 21

Conti… q Procedure After completion of OQ initiate the PQ of FBD. ü The effectiveness of drying will be qualified by determining reduction of % moisture content in drying process. ü 3 batches/ lots of any product will be taken for PQ of FBD. ü At least 2. 0 gm of sample is sampled for % MC check from the top, middle and bottom trays and will be reported ü 22

Conti… In case of any deviation inform to department head for necessary action ü Document the deviation details ü Deviation is acceptable or not will be decided -if yes -if not ü 23

Conti… q Acceptance criteria ü The reduction in moisture content after drying should be as per the specification in the BMR ü % RSD of LOD should not be more than 6 % ü The equipment should produce intended outputs with respect to quality & quantity consistently 24

Conti… q Revalidation Criteria: v The equipment shall be revalidated if; ü Location of the equipment is changed. ü There is change of spare/ parts, major maintenance or breakdown that have a direct effect on the performance of the equipment ü At normal revalidation schedule. 25

PROCEDURE FOR DRYING EFFICACY STUDY IN FLUIDIZED BED DRYER: Ensure the cleaning of machine ü Load the wet mass in the FBD product container ü Set the process time & outlet temperature and run the FBD. ü After completion of drying take out FBD bowl and collect the sample ü At least 2. 0 gm of sample is sampled for % MC check from the top, middle and bottom trays and will be reported ü 26

Conti… q Sampling Procedure: Ware nose mask, hand gloves before sampling. ü Label the sample bag with details as Product name, stage, date, time and sign ü Collect app. 2. 0 gms of dried material composite sample in poly bag as per location shown ü Record the details of analysis. ü 27

Validation of Tray dryer 28

TRAY DRYER 29

TRAY DRYER CONTROL PARAMETERS Fixed Variable (monitor) Response (Test) ØTrays ØInlet/exhaust air temperature ØProduct temperature ØDrying time ØAir volume ØHumidity of incoming air ØHumidity of exhaust air ØParticle size distribution ØDensities ØLoss on drying ØAssay 30

INSTALLATION QUALIFICATION(IQ) q Procedure: Selection criteria shall be defined and based on specific function to be carried out by the machine & its efficiency. ü Requirement of accessories shall be decided & listed out. ü Supplier or manufacturer selection ü 31

Conti… q Purchase Details: ü The purchase order no. & date shall be checked ü The accessories & their spare parts if any shall be checked as per purchase order ü The delivery period shall be as per purchase order ü Supplier or manufacturer name & address shall be checked ü Any deviation observed should be informed to the supplier or manufacturer 32

Conti… q Details of the Equipment ü Equipment name, make & model no. shall be noted down ü In-house identification no. shall be allocated ü Location for installation shall be decided ü Utilities required shall be listed down 33

Conti… q Installation Procedure: ü After checking all the specifications as mentioned in the selection criteria, service engineer of the manufacturer shall be called for commissioning, if necessary. ü Authorized validation team shall carry out installation ü Department Head of production, QA & engineering shall evaluate installation report 34

Conti… q Acceptance Criteria For IQ ü Fulfill the selection criteria & its purpose of Application ü The equipment shall be as per purchase order ü Accessories received shall be as per purchase order ü Should meet pre-selected design parameters ü Manufacturer/supplier shall provide complete equipment manual ü Material of construction shall be as per purchase order 35

OPERATIONAL QUALIFICATION (OQ) q Training record ü Before initiating OQ ensure that SOP for Cleaning and operation of Tray dryer is available. q Purpose: To train the qualification team for performing OQ 36

Conti… q Procedure Initiate the actual operation of the TD to ensure that machine is operating within specification. ü Check the OQ parameters against their specifications. ü Observe the functioning of all controls available on control panel ü Record the observation ü 37

Conti… Acceptance criteria ü All operating inputs provided on the equipment when tested shall-successfully comply -meet tolerance limit ü The equipment should successfully perform when operated as per SOP ü Critical gauges/indicators provided on the equipment- --calibrated ü The equipment when operated shall not - produce abnormal sound - show any discrepancy in its smooth operation. q 38

PERFORMANCE QUALIFICATION(PQ) 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 ü 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. ü 39

Conti… q Procedure After completion of OQ initiate the PQ of TD ü The effectiveness of drying will be qualified by determining reduction of % moisture content in drying process. ü 3 batches/ lots of any product will be taken for PQ of TD ü At least 2. 0 gm of sample is sampled for % MC check from the top, middle and bottom trays and will be reported ü 40

41

Conti… In case of any deviation inform to department head for necessary action ü Document the deviation details ü Deviation is acceptable or not will be decided -if yes -if not ü 42

Conti… q Acceptance criteria ü Temperature difference between all thermocouples and set temperature should not differ by more than 5 °C. ü The reduction in moisture content after drying should be as per the specification in the BMR ü % RSD of LOD should not be more than 6 % ü The equipment should produce intended outputs with respect to quality & quantity consistently 43

REFERENCES Berry I. R. , and Nash R. A. , ”Pharmaceutical Process validation” second edition, revised and expanded; Marcel Dekker series; 83 -110. 44

SEMINAR OPEN FOR DISCUSSION 45

46