Material Requisition Procedure, Purpose:

Material Requisition Procedure, To lay down the procedure for raising Requisition of Material to the Ware-House.

Material Requisition Procedure, Scope:

This SOP is applicable for the Production Area  of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the laid down procedure

Manager, Production

[][]To Implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Material Requisition shall be raised in following cases.
[][]On line rejection: If approved raw material or packing material issued for the batch is rejected on line due to quality defects like black particles in raw material, hard lumps, smudged printing or no  printing on printed materials like foil, carton, insert, label and shipper and color variation beyond acceptable shade.
[][]Material consumed more than standard: In case dispensed raw material is compensated due to spillage, spray pipe leakage during coating, excess coating material and packaging materials required for recovery addition, excess foil consumption during blister pack machine setting, excess carton consumption during manual cartooning, printing problem of carton, catch cover, insert and shipper carton.
[][]Production Executive shall raise ‘Material Requisition’ (Annexure-I) by writing all details with reason in the ‘Remarks’ column and shall sign in ‘Requisitioned by’ row.
[][]Material Requisition (MR) shall have duplicate copy. First copy shall be mentioned as ‘Ware-House Copy’ at right top corner of Material Requisition form. Second copy shall be mentioned as ‘Batch Record Copy’ at right top corner of Material Requisition form.
[][]Head of Quality Assurance (QA) or his/her designate shall justify the reason for MR and will approve accordingly.
[][]Approved Material Requisition shall be sent to dispensing for Issuance.
[][]After Issuance of materials ‘Batch Record’ copy shall be attached with Batch Manufacturing Record (BMR) & Batch Packaging Record (BPR) and ‘Ware-House Copy’ shall be sent to Ware-House for stock adjustment purpose.

Annexure:

Annexure I –Material Requisition.

Equipment Logbook, Purpose:

Equipment Logbook, To lay down the procedure for Maintaining Record of Equipment Usage, break-down, cleaning and change over functions during all Manufacturing Activities.

Equipment Logbook, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]Equipment : The implement, which is used at an Operation or Activity.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check laid down procedure

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Use of Equipment Log Book :

[][]Equipment Log Book is to record equipment usage maintenance and cleaning record. The records are maintained to trace back the previous history.
[][]Maintain individual ‘Equipment Log Book’ (Annexure-I) for each equipment.
[][]Equipment log book format is divided in 05 parts
[][]Product Information
[][]Equipment usage details
[][]Cleaning details
[][]Change Over details
[][]Inspection and Approval
[][]Product Information
[][]Product name, Batch no., Batch size shall be recorded in log book.
[][]Each book is dedicated for each equipment
[][]Equipment usage details
[][]Product start time and end time shall be recorded in log book.
[][]This is applicable for each batch activity.
[][]Record the activity / batch operations shift wise in log book.

[][]All break times like Lunch time, Tea time, machine stoppage due to breakdown, machine stoppage at the end of the shift or day and machine stoppage due to power failure, only if restart time is more than 5 minutes.

Equipment cleaning details

[][]The equipment cleaning is applicable in following events.
[][]Batch changeover of the same product and different product.
[][]After cleaning if cleaned equipment is kept idle for more than defined hold time which shall be studied and incorporated in respective equipment SOP.
[][]If equipment is relocated /shifted within the facility as well as for new equipment.
[][]In case of cleaning after maintenance activity.
[][]In case of cleaning after area fumigation.
[][]After usage of equipment, clean it as per the procedure defined in respective equipment SOP.
[][]The type of cleaning shall be mentioned in specified column in log book.
[][]After cleaning is completed, inform QA (Quality Assurance) to inspect and approve for next activity.

Change Over Details :

[][]Change Over is applicable in following events.
[][]Change over is done for product to product change.
[][]Start and end time shall be mentioned in specified column in log book.
[][]After change over is completed, Executive, Production check setting of machine & will take step for next activity.

Inspection and Approval before usage

[][]Before usage Equipment, it is to be checked for its suitability for next activity by Executive, Production and then inspected and approved by Executive, Quality Compliance.
If production is on campaign basis, after every 10th batch, cleaning activity is carried out and details are recorded.
[][]During campaign of same product, equipment shall be cleaned as per respective equipment SOP but prior to start next batch approval shall be taken by Executive, Quality Compliance.

Additional Information at the Remarks Column

[][]Throughout the working day operation, if the operating machine turns ‘Stop’ by either mechanical or electrical reasons, note the total down time for a day at the Remarks column.

Annexure:

Annexure I – Equipment Log Book.

Line Clearance , Purpose:

Line Clearance , To lay down the procedure for Line Clearance at Production Area during Product to Product changeover and Batch to Batch changeover.

Line Clearance , Scope:

This SOP is applicable for the Production Area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure.

Executive, Production

[][]To monitor and check the laid down procedure.

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precautions:

[][]Ensure the proper safety instructions are followed.
[][]Ensure that no previous product is available in the area.

Line Clearance during Product to Product Changeover

[][]Ensure that all utility lines like compressed air line, steam line, electrical fixtures, air inlet ducts, return air risers, potable water and purified water lines are cleaned and no visible traces of product are present.
[][]Ensure that door, floor, walls and ceiling are cleaned.
[][]Ensure that area cleaning activity is recorded in ‘Room Cleaning Log book’
[][]Ensure that all equipments in the area are cleaned according to their respective SOPs and no traces of previous product are visible within the equipment.
[][]Check and ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’
[][]Ensure that Span between equipment usage and cleaning is not more than seventy two hours.
[][]Ensure that Balances in the production area are cleaned and accuracy check is done once daily.
[][]Ensure that production utensils like scoops, spatula, pallets, BMR table, tool boxes etc. are cleaned as per procedure.
[][]Ensure that all equipments are labeled as ‘CLEANED’
[][]Ensure that fresh set of gowns are issued to concerned operators.
[][]Ensure that proper environmental condition is maintained in the area and the records of the same are maintained in the specified formats.
[][]Ensure the correctness of Batch Manufacturing Record / Batch Packaging Record.

Line Clearance during Batch to Batch Changeover

[][]Ensure that previous batch material is removed from the production area.
[][]Ensure that all the equipment and their spares are cleaned according to their respective SOPs.
[][]Ensure that equipment cleaning activity is recorded in respective ‘Equipment Log Book’.
[][]Ensure that floor is cleaned using vacuum cleaner and no visible traces of the previous batch material on the floor.

Annexure:

[][]N/A

Digital Weighing Balance, Purpose:

Digital Weighing Balance, To lay down the procedure for operation, accuracy check and cleaning of the weighing balances at the Production Area.

Digital Weighing Balance, Scope:

This SOP is applicable for 320 g & 60 Kg weighing balance for weighing of materials at the Production Area of XX Pharmaceuticals Ltd.

Definition / Abbreviation:

N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution:

[][]Do not pour liquids on the weighing platform.
[][]Do not use solvents to clean the platform.
[][]Ensure balance is clean before use, including its surrounding area.
[][]Check and ensure the due date of calibration before use.
[][]Check and ensure the level indicator of weighing balance is in the middle, if applicable.
[][]Use hand gloves to hold standard weights for function check and calibration.

Daily Performance Check :

[][]Plug in the power cord.
[][]Level the balance using leveling feet so that air bubble is centered within circle of level indicator.
[][]TO turn the balance ON, short pressing the <O/T> key.
[][]Wait a while so that the stability indicator [*] is displayed.
[][]Zero the balance by pressing the >O/T> key.
[][]Press the 100 mg mass at the centre of the platform and record the value displayed in the daily balance check logbook.
[][]Press the 100 g mass at the centre of the platform and record the value displayed.
[][]Press the 200 g mass at the centre of the platform and record the value displayed.
[][]Print the results by pressing print ( ) button if necessary.
[][]Record the value of those weights in Log Book for ‘Daily Accuracy Check’ (Annexure – I).
[][]If any displayed value is out of acceptable limit, label the balance “DO Not Use” and inform the QA Executive for immediate calibration of the balance.
[][]Balance accuracy check must be performed at the starting of the day.

[][]If the factory remains close for the day(s), put the comments in the remarks column against that day(s) at the day of factory resume.

Operation of 320 g Balances of Mettler Toledo :

To start up:

[][]Level and adjust at each time it is moved to a new location. The balance is exactly horizontal when the air bubble is in the middle of the level glass. Adjust the two front leveling feet appropriately until the air bubble comes to rest exactly in the middle of the glass.
[][]Plug the AC adapter and connect the power supply. Connect the printer to the balance (if available).
[][]Switch on the printer using I/O switch.
[][]Press On/Off ( ) button to on the Electric Analytical Balance. Display will show 0.000g.
[][]Convert the weighing unit from g into mg, press scroll down ( ) button if necessary.
[][]Allow the balance to warm up to enable it to adapt itself to the ambient condition.
[][]Long press for menu ( ) button and select ‘BASIC’ by single press Enter button ( ).
[][]Set date, time and unit using – /+ keys and Enter button ( ) and save the settings using ( ) button.
[][]Press cancel (C) button to return come out of that ‘BASIC’ option and return to its main menu.

[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Weighing:

[][]Check the machine is clean and calibrated. Then remove all loads from weighing pan.
[][]When zero (0.000 g) reading is displayed, the balance is ready for operation. If the display shows greater than or less than zero, press tare ( O/T ) button to tare the balance.
[][]If the balance is not in the weighing mode, press and hold the ( ) key down until ‘WEIGHING’ in the display.

[][]Use handle/coupling element for the operation of the draft shield door of the both side of the instrument.
[][]Open right/left/upper sliding window of the instrument.
[][]Place empty container/weighing paper on the pan of the balance. Close the sliding window.
[][]The weight is displayed. Allow the reading to stabilize and wait until the instability detector (O) disappears from the left side of the display and the stability beep sounds.
[][]Press tare ( O/T ) button to tare the balance. When zero (0.000 g) reading is displayed, the balance is ready for weighing.
[][]The weighing-in aid is a dynamic graphic indicator which shows the used amount of the total weighing range. It can be recognized at a glance when the load on the balance approaches the maximum load.
[][]Add weighing sample (Maximum 320g) on the container/weighing paper using weighing spoon. Close the sliding window. The net weight is now displayed.
[][]Allow the reading to stabilize and wait until the instability detector (O) disappears for the display and the stability beep sounds.
[][]To get printout of the weight, press print ( ) button.

[][]For performing another weighing press tare ( O/T ) button to tare the balance and follow steps from previous steps To increase or decrease digit, press display resolution ( ) button.
[][]Finally, press and hold On/Off button ( ) button until ‘SHUT OFF’ shows on the display.

Calibration:

Internal Calibration:

[][]Manual Adjustment with Internal weight:
[][]Long press menu ( ) button and press scroll down ( ) button to go to ‘ADVANCED’ option.
[][]Select ‘ADVANCED’ by pressing Enter ( ) button.
[][]Press scroll down ( ) button once to select ‘CAL’ option by pressing Enter ( ) button.
[][]Then select ‘ADJ. INT’ using scroll down ( ) button and then press Enter ( ) button.
[][]Press cancel (C) twice and save the settings if required by scrolling down ( ) button and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘Internal Adjustment’.
[][]The balance adjusts itself automatically. The adjusting is finished when the message “ADJ.DONE” appears briefly on the display. The balance returns to the last active application and is ready for operation.

[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

External Calibration:

[][]Manual Adjustment with External weight:
[][]Follow the instruction from previous steps
[][]Select ‘ADJ. EXT’ by using scroll down ( ) and then press Enter ( ) button.
[][]Set the adjustment weight (100g) by using -/+ key for External Calibration and press Enter ( ) button.

[][]Then press cancel (C) button twice and save the settings if required by using -/+ key and press Enter ( ) button and then return to its main menu.
[][]Unload weighing pan Press and hold calibration ( ) button to execute ‘External Adjustment’.
[][]The required predefined adjustment weight value flashes on the display.
[][]Place adjustment certified weight on the center of pan. The balance adjusts itself automatically.
[][]When ‘0.00 g’ flashes, remove the adjustment weight.
[][]The adjustment is finished when the message ‘ADJ DONE’ appears briefly on the display. The balance returns to the last active application and is ready for operation.
[][]After adjustment, the result of the calibration will be printed out automatically or press print ( ) button for print copy.

Operation of 60 kg Balances of Mettler Toledo:

[][]Using an Empty container for Weighing:
[][]Press the zero button.
[][]Place an empty container on the scale platform.
[][]Press the Tare button.
[][]Fill the container with material to be weighed.

[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]To clear a tare weight (with the scale in the net weight mode and a tare weight previously entered), press the Clear key (C).

Without using an Empty container for Weighing:

[][]Press the zero button.
[][]Place the material to be weighed on the scale platform.
[][]The terminal will display the net weight and the NET cursor will light up. Allow the reading to be stable. Write down the reading.
[][]Perform the ‘Daily Accuracy Check’ (Annexure – I) at the starting of the day.

Acceptance Criteria:

[][]The observed weights should be within ± 0.1% of the certified standard weights.
[][]If the acceptance criteria are not satisfied, follow the procedure for Handling of out of calibration for instrument & equipment.

Calibration:

[][]Perform the routine calibration half year. Recalibration is required in the following cases :
[][]After any minor service has been done or replacement of parts.
[][]When the software or firmware has been upgraded or changed.
[][]If daily check fails

Cleaning:

[][]Place the status label ‘TO BE CLEANED’  on the equipment.
[][]Switch off the balance and unplug from the socket.
[][]Remove all objects from the weighing platform of balance.
[][]Lift up and remove the weighing pan in such a way that there is no damage in weighing system.
[][]Clean the pan including underside using a piece of dry cloth. Use wet cloth and finally clean with disinfection solution
[][]Wipe the display, switch board and cables with dry cloth.
[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’  label on the equipment after approval from Quality Compliance.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure: Digital Weighing Balance

Annexure I – Daily Accuracy Check.

Monitoring of Room Condition, Purpose:

Monitoring of Room Condition, To lay down the procedure for monitoring of Temperature, Relative Humidity (%) and Pressure Gradient at the Production Area.

Monitoring of Room Condition, Scope:

This SOP is applicable for the Production Area of General Block of the XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows :

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the procedure is followed

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure :

Precaution :

[][]Do not use a new hygrometer unless it is calibrated.
[][]When any hygrometer is shifted from one location to another, allow to stabilize the device prior to record the temperature / Relative Humidity (%).
[][]Check the due date of calibration of the hygrometer and magnehelic gauge before taking reading.
[][]Ensure that temperature and Relative Humidity (%) readings are taken before going to operation.

[][]Temperature and Relative Humidity (%) (using Digital Hygrometer)
[][]Ensure that no dust is accumulated over the sensor.
[][]Read the temperature and relative humidity (%) values displayed on the screen of digital/analog hygrometer and record in ‘Temperature, Relative Humidity (%) & Pressure Gradient Records’ (Annexure-I).
[][]Acceptance Criteria:

Area	Temperature	Relative Humidity (%)
Dispensing, Material Staging, Dispensed Material Staging, D Corridor, Wash Bay, Clean Equipment, Broken Bulk, FBD Bag Store, Solution Preparation, Clean Equipment, Encapsulation, WIP Granules, WIP Tablet & Capsules, Coating, Tools Storage, Office Room, Coating Solution Preparation, D Dress Washing & Drying, Foil/Film Staging, Blister Packaging and Dry Syrup Filling & Sealing.	Not more than (NMT) 25°C	Not more than (NMT) 60 %
Granulation, Blending, Tablet Compression.	Not more than (NMT) 25°C	Not more than (NMT) 45%

Pressure Gradient

[][]Read the pressure differential from magnehelic gauge provided and record.
[][]If the reading is not within limit, check whether all the doors are closed.
[][]Observe the second reading.
[][]Even if the second reading is not within the limit, inform the Engineering department for corrective action.

Area	Pressure Differential
Processing Units Negative with respect to corridor (i.e. Air Flow is from corridor to processing unit)	10 – 20 Pascal
Wash Bay Positive with respect to Corridor (i.e. Air Flow is from Wash Bay to Corridor)	10 – 20 Pascal

Frequency

[][]Twice in a shift, first before starting the operation and second after four hours.
[][]If the reading is not within limit at any time of operation, inform the Engineering department immediately and take following steps in different areas.
[][]At Dispensing area stop weighing process, close the bags / high density polyethylene (HDPE) drums of raw materials.
[][]At Granulation area, stop transfer process of materials if running and close the SS / HDPE container with lid.
[][]Do not discharge if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Blending area, continue blending process if already running.
[][]At Compression area, stop operation and close the tablet SS/HDPE container lid. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Encapsulation area, stop operation and close the capsule SS/HDPE container lid. Do not keep the granules / pellets in the hopper during overnight. Empty the hopper and close the lid of SS/ HDPE container.

[][]At Coating area, continue operation if already running, otherwise stop operation. Do not unload if temperature and relative humidity (%) or pressure gradient are not within limit.
[][]At Powder filling area, stop the operation. Do not keep the granules in the hopper during overnight.
[][]Empty the hopper and close the lid of SS / HDPE container.
[][]At Blister Packing area, close the lid of tablet / capsule container, close the hopper with lid and stop further operation.

Annexure:

Annexure I – Room Condition Monitoring Logbook

Production area Cleaning Procedure, Purpose:

Production area Cleaning Procedure, To lay down the procedure for effective Cleaning of Production area during Product to Product change over, Batch to Batch change over and at the end of day’s operation.

Production area Cleaning Procedure, Scope:

This SOP is applicable for the Production Area of  XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

[][]The Roles and Responsibilities are as follows:

Operator

[][]To follow the laid down procedure

Executive, Production

[][]To monitor and check the cleanliness of area

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

Precaution :

[][]Do not clean/disinfect the area when the process is running.
[][]Keep the cleaning agents at the designated place only with proper labels.
[][]Ensure that after usage the wet mops are washed and hanged in hanger in cleaner store &allowed to dry. Ensure other cleaning tools are also hanged in hanger after use.
[][]After use of cleaning agent wash hands, feet and fingers thoroughly with soap & plenty of water.
[][]Ensure that during cleaning all the product containers are closed.
[][]Check and ensure that disinfectant solution prepared is not stored for use for the next day and the residue is discarded by pouring into drain.
[][]At least two different disinfectants are to be used alternatively on weekly basis.
[][]Do not mop the floor after keeping ‘Cleaned’ equipment in clean equipment storage room.

Cleaning Tools / Agents

[][]Portable vacuum cleaner
[][]Cloth & wiper
[][]Potable water and Purified water
[][]Glass Cleaning agent: ‘Clear View’ (Brand Name)
[][]Disinfectant Savlon (Cetrimide + Chlorhexidine Gluconate) / Dettol (Chloroxylenol) / Clotec (Hypochloride).

Preparation of 2.5 % v/v Savlon/ Dettol/Clotec

[][]To make 10 L disinfectant solution take 0.250 L Cetrimide + Chlorhexidine Gluconate/ Chloroxylenol / Hypochloride in freshly collected purified water to make up volume up to 10 L.
[][]Stir well to mix the solution properly.
[][]Prepare the disinfectant solution separately in separate bucket for use in different floor.
[][]Maintain the ‘Disinfectant Solution Preparation Record’ (Annexure – I).

Product to Product Cleaning Procedure (Type – A Cleaning) for Production Area

[][]Type – A cleaning is defined as cleaning procedure followed during product to product changeover.
[][]If the unit/equipment is used for same product it has to be cleaned after 72 hours.
[][]Place the status label ‘TO BE CLEANED’ (As per Form No. SOP/QCOM/008/XI) in the Area.
[][]Clean the ceiling, walls, outer surface of light fixtures, supply diffusers (SD) and return grills (RG) first with portable Vacuum cleaner to remove loose dust using a platform trolley, then with wet mop.
[][]Clean the machine/equipment in Production area as per SOP.
[][]Clean the doors, compressed air lines and other service lines with dry cloth.
[][]Clean the glasses with ‘Clear View’ solution and wipe.
[][]Clean the control panels, electrical wires with dry cloth.
[][]Clean toolbox, Batch Manufacturing Record table, log books, SOP holders, hygrometer, stool / chair with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.
[][]Ensure after inspection for absence of any residue of previous product. If any residue of previous product or extraneous matter is found, re-clean the area using above procedure until the area is free of any residue/ extraneous matter.

[][]Remove ‘TO BE CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the cleaned area after approval from Quality Compliance.
[][]Record the cleaning activity in ‘Room Cleaning Log Book’ (Annexure – II).

Frequency of Cleaning

[][]During product to product change over.
[][]After 3 days or 72 hours from the date of use of the equipment or area. If any batch is running and 72 hours time exceeds during the batch running period, cleaning shall be done after the batch is finished. If 72 hours time exceeds after cleaning and the equipment or area is not used, use the equipment or area after performing B-type cleaning.

Batch to Batch Cleaning (Type-B Cleaning) for Production area

[][]Type – B cleaning is defined as cleaning procedure followed during batch to batch changeover of a
same product.
[][]Place the equipment status label ‘PARTIALLY CLEANED’ (As per Form No. SOP/QCOM/008/X) in the area.
[][]First clean the floor, ceiling, walls, outer surface of light fixtures, supply diffusers (SD), return grills, (RG) doors and equipment with portable vacuum cleaner to remove the loose dust. [][]Finally clean the floor with wet mop.
[][]Remove ‘PARTIALLY CLEANED’ and affix ‘CLEANED’ (As per Form No. SOP/QCOM/008/IX) label in the area.
[][]Record the cleaning activity in Room Cleaning Log Book.
[][]Frequency of Cleaning
[][]During batch to batch change over

[][]Cleaning at the End of Day’s Operation
[][]Clean external parts of the machine, and operating panel with dry cloth.
[][]Clean the floor first with dry mop, then with potable water and mop with disinfectant solution. Finally clean with purified water.

Annexure:

Annexure I – Disinfectant Solution Preparation Record.
Annexure II – Room Cleaning Log Book.