Category: Production SOP

SOP Title: Start Up of Production Activity After Long Period

1. Objective:

To define procedure for start up of production activity after long period.

2. Scope:

This SOP is applicable to start up of production activities in Production Department, which is non-operational for a period of more than four weeks.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedure for in-process checks described in the SOP.
   • Quality Assurance Department: To ensure the products meets the specification. To review and approve the SOP.
   • Engineering Department: To perform the Preventive Maintenance and Calibration activity of the instruments.
4. Accountability:

Head, Production  Department. Head, QA Department.

5. Procedure:
   • Definition:
     • Production Associate: Executive or Operator of Production Department or any personnel trained to perform duties as per this SOP.
     • Quality Assurance Associate: Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
     • Engineering Associate: Executive or operator of Engineering Department trained to perform duties as per this SOP.
   • Procedure

	Precautions:
5.2.1	Check the civil / electrical connection status of the area i.e.  Flooring, ceiling, wiring, lighting, painting, etc. for its correctness.
5.2.2	Check the status of all equipments and accessories for its smooth operation and safety of devices.
5.3	Operation:
5.3.1	Clean the area as per Sop “Cleaning and Sanitation of Production Area.
5.3.2	Check the filters of Air Handling Unit visually for proper fitting, service lines of water, compressed air, steam and dust collection chamber. Clean as per their respective SOP.
5.3.3	Clean all equipment and accessories as per respective SOP and get it certified by Quality Assurance.
5.3.4	Fumigate the area as per SOP and sanitise the area using regular disinfectant solutions.
5.3.5	After fumigation, environmental monitoring of the area should be done.
5.3.6	Check visually the area cleanliness and equipment by taking rinse sample and get it certified by Quality Assurance.
5.3.7	Calibrate the all equipment before use as per the respective SOP. Record the cleaning, calibration and other environmental activity in the respective log / format.

 

6. Abbreviation:

Abbreviation	Expansion
PD	Production Department
TAB	Tablet
%	Percent
SOP	Standard Operating Procedure
QA	Quality Assurance

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Operation and Cleaning of Stainless  Steel Trolley

1. Objective:

To define procedure for Operation and Cleaning of Stainless Steel Trolley.

2. Scope:

This SOP is applicable to Stainless Steel Trolley used for transferring of material, accessories and equipment in the production section.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedures laid down for the operation and cleaning and to support for Preventive Maintenance of Stainless Steel Trolley.
   • Engineering Department: To perform the preventive maintenance of Stainless Steel Trolley.
   • Quality Assurance Department: To provide line clearance prior to operation. To approve the Preventive Maintenance reports. To review and approve the SOP and Annexure.
4. Accountability:

Head, Production Department,  Head, Engineering Department and Head Quality Assurance.

 

5. Procedure:
   • Definition:
     • Production Associate: Executive or Operator of Production Department or any personnel trained to perform duties as per this SOP.
     • Quality Assurance Associate: Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
     • Engineering Associate: Executive or operator of Engineering Department trained to perform duties as per this SOP.
     • Type A Cleaning: Dry cleaning with clean lint free cloth / Vacuum in the following cases,
       • Remove the previous batch residue.
       • During end of the shift.
       • Before starting the next batch of the same product.
       • Prior to execution of higher strength batches, after the execution of lower strength batches of the same product.
     • Type B Cleaning: Wet cleaning by using soap solution in the following cases
       • Removal of traces of the previous product, and is ensured by testing rinse /swab sample of the cleaned equipment.
       • Change in product.
       • After seven days of cleaning before use, if trolley is not in used after cleaning.
       • After replacement or repair of any product contact part.
     • Cleaning Solution: 1 ml of Teepol (soap solution) in 1000 ml of potable water (0.1% v/v)
     • Breakdown: Any activity leading to operation of machine other than the set parameters and / or unusual sound or vibration observed in the machine.
     • Preventive Maintenance: Maintenance activity performed to ensure that the equipment will function smoothly and to avoid breakdowns. These activities are performed, quarterly and half
   • Procedure

	Precautions
5.2.1	Do not over load the trolley more than the 75 kilogram.
5.2.2	Check that, trolley wheels are working properly by moving empty trolley on floor
5.2.3	Check visually, trolley wheels are free from any threads / sticky material.
5.2.4	Do not stand or sit on the trolley or do not use for personnel movement.
5.3	Operation
5.3.1	Before use ensure that, trolley is clean and smooth moment of wheels is free by checking backward and forward movement of the empty trolley.
5.3.2	Take the trolley from the dedicated area and hold the trolley with handle provided on the upper part of the trolley.
5.3.3	Keep the material / product to be transferred on the trolley within the capacity of the trolley.
5.3.4	Push the trolley forward by holding the handle of the trolley.
5.3.5	During passing from the door, one person should hold the door to open, and then pass from the door to the next area.
5.3.6	After reaching the shifting/transferring place, lift the material from the trolley platform by hand and slowly keep in the required place.
5.3.7	Clean the trolley with wheel by moist clean duster before transferring to one area to another area.
5.3.8	After using keep the trolley in the dedicated place.
5.3.9	After completion of activity, label the trolley as “To be Type A cleaned” or “To be Type B Cleaned”.
5.4	Type A Cleaning
5.4.1	Clean the platform, handle and base of the trolley by wiping with clean dry duster.
5.4.2	Clean the trolley wheels with moist duster by tilting the trolley and rotating the wheels manually.
5.4.3	Ensure the cleanliness of the trolley usually for absence of dust / powder
5.4.4	Check the wheels for absence of any adhered sticky powder / treads and affix “Type A Cleaned’ label on the trolley.
	Frequency: During batch changeover and moving from one area to another area.
5.5	Type B Cleaning
5.5.1	Clean the platform, handle, wheels and base of the trolley by wiping with clean dry duster.
5.5.2	Wash the trolley platform, handle, wheels with 10-15 litres of potable water.
5.5.3	Clean the trolley platform, base, handle with 0.1% soap (teepol) solution then wash with     10-15 litres of potable water to remove the traces of soap solution.
5.5.4	Tilt the trolley and clean the wheels with 0.1 % soap (teepol) solution by rotating the wheels then wash with 5-7 litres of potable water.
5.5.5	Keep the trolley on wet duster and move the trolley  forward and back ward 4- 5 times to remove the any adhered material to the trolley wheels.
5.5.6	Ensure the cleanliness by visually and dry the trolley with clean dry duster.
5.5.7	After successful completion of cleaning process, label  as “Type B Cleaned”.
	Frequency of cleaning: 1. During product change over 2. After any major maintenance to the trolley.
5.6	Breakdown
5.6.1	If breakdown occurs during operation, hold the  transferring activity and unload the material /container from the trolley. Inform to the Head Production.
5.6.2	Fill the “Complaint Note” and submit to Engineering Department.
5.6.3	Fill the “Incident Report” and submit to Quality Assurance Department.
5.6.4	Store the unloaded capsules in suitable SS closed container.
5.6.5	If breakdown occurs prior to start of operation, follow step 5.6.2.
5.6.6	After completion of repairs, the operations can be resumed. Perform “Type A or Type B” cleaning.
5.6.7	Collect and file a copy of the “Complaint Note” certifying that the repair works have been successfully completed.
5.7	Preventive Maintenance
5.7.1	Perform the preventive maintenance as per Annexure.
5.7.2	If preventive maintenance activity is outsourced, the values are to be transcribed in the Annexure, and external party certificate to be attached.
5.7.3	Attach the preventive maintenance label on the equipment.

 

6. Abbreviation:

Abbreviation	Expansion
SOP	Standard Operating Procedure
PDD	Production Department
PKG	Packing
E	Equipment
TAB	Tablet
%	Percent
QAD	Quality Assurance Department
QA	Quality Assurance
v/v	Volume by Volume

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Operation and Calibration of Rapid Mixer Granulator (RMG)

1. Objective:

To define procedures for Operation, Cleaning, Preventive Maintenance and Calibration of Rapid Mixer Granulator.

2. Scope:

This SOP is applicable to Rapid Mixer Granulator used for dry mixing and granulation process in granulation area.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedures laid down for the operation and cleaning and to support for Preventive Maintenance and Calibration of Rapid Mixer Granulator.
   • Engineering Department: To perform the Preventive Maintenance and Calibration of Rapid Mixer Granulator
   • Quality Control Department: To analyse and report the swab samples.
   • Quality Assurance Department: To provide line clearance prior to operation. To collect the swab/rinse samples. To approve the Preventive Maintenance and Calibration reports. To review and approve the SOP and Annexure
4. Accountability:

Head, Production Department, Head, Engineering Department and Head, Quality Assurance

5. Procedure:
   • Definition:
     • Production Associate: Executive or operator of Production Department or any personnel trained to perform duties as per this SOP
     • Quality Assurance Associate: Executive of Quality Assurance department or any personnel trained to perform duties as per this SOP
     • Quality Control Associate: Executive of QC department trained to perform duties as per this SOP.
     • Engineering Associate: Executive or operator of engineering department trained to perform duties as per this SOP.
     • Type A Cleaning: Dry cleaning with clean lint free cloth in the following cases
       • Remove the previous batch residue.
       • During end of the shift.
       • Before starting the next batch of the same product
       • Prior to execution of higher strength batches, after the execution of lower strength batches of the same product
     • Type B Cleaning: Wet cleaning by using soap solution in the following cases
       • Removal of traces of the previous product, and is ensured by testing rinse /swab sample of the cleaned equipment.
       • Change in product
       • Prior to execution of lower strength batches, after the execution of higher strength batches of the same product
       • After continuous five batches of the same product
       • After seven days of cleaning before use, if equipment is not in use
       • Change in colour in granulation stage even if the product is same
       • After replacement or repair of any product contact part
     • Cleaning Solution: 1 ml of Teepol ( soap solution) in 1000 ml of potable water (0.1% v/v)
     • Breakdown: Any activity leading to operation of machine other than the set parameters and / or unusual sound or vibration observed in the machine
     • Preventive Maintenance: Maintenance activity performed to ensure that the equipment will function smoothly and to avoid breakdowns. These activities are performed monthly, quarterly and half yearly.
     • Calibration: Tests performed to ensure that the equipment is functioning as per set parameters. These test are performed half yearly, yearly and also after repair or replacement of parts coming in direct contact with product
   • Procedure

	Precautions
5.2.1	Ensure that the limit switch is working properly by switching “ON” the Rapid Mixer Granulator and by lifting and closing of lid.
5.2.2	Do not touch the moving parts or do not put hand during running the machine.
5.2.3	During manual scrapping, loading, unloading put “OFF” the main supply of the machine.
5.2.4	Ensure that the discharge valve is operating properly by visual observation from inside the RMG.
5.2.5	Ensure that the validity of Calibration and Preventive Maintenance before starting any operations.
	Set Up / Assembling
5.2.6	Ensure that the equipment has a “cleaned” status label.
5.2.7	Place the impeller blade at the bottom of the bowl and secure it with a lock nut.
5.2.8	Place the chopper blade at the side of bowl and secure it with a lock nut.
5.2.9	Place the vent filter on the lid of the vessel by fasting the screw.
	Operation
5.2.10	Before starting the operation make sure that the line clearance is taken and recorded in the BMR Record the activity in the equipment log book.
5.2.11	Open the compressed air supply valve, the air pressure gauge will display the actual air pressure in kg/cm2 . Note: The compressed air should be more than 4 Kg/cm2 .
5.2.12	Switch “ON” the main electrical supply line followed by switching “ON” the electrical line of the RMG panel by rotating knob from “I” position to right hand side. The main motor current and the chopper motor current will be displayed on the panel.
5.2.13	Open the lid of the machine by unlocking four clamps provided in the RMG Note: Ensure that, the vent filter is clean by checking pores visually.
5.2.14	Place the FBD bowl or container below the discharge port during the   operation of machine to avoid the spillage of the product by non-functioning of the valve.
5.2.15	Load the sifted raw material sequentially as mentioned in BMR.
5.2.16	Close the lid of the RMG properly by locking clamps. Note: if the limit switch is not pressed properly the machine will not start.
5.2.17	Set the required mixing time on the timer as mentioned in BMR. The number in timer represents minutes. Example, “3” in the timer indicates 3 minutes
5.2.18	Dry mix the contents of the RMG. As mentioned in BMR set the speeds for impeller and chopper. Push the impeller button (yellow colour for slow speed and green coloured for high speed) Rotate the green colour chopper button (right side for high speed and left side for low speed). Record the time and speed of impeller and chopper in BMR Record the ampere display in BMR. The impeller slow speed is 75 rpm and high speed is 150 rpm. The chopper slow speed is 750 rpm and high speed is 1500 rpm
5.2.19	Granulate the contents of the RMG by adding the binder solution / paste by opening the granulation port on the lid. Record the time and speed of impeller and chopper in BMR. Record the ampere display in BMR .
5.2.20	Knead the wet mass if needed to achieve granules of desired consistency. Record the time and speed of impeller and chopper in BMR. Record the ampere display in BMR.
5.2.21	Discharge the contents of the RMG by pressing the discharge button (green coloured) to collect the material in FBD bowl. Note: Ensure that all the contents of the RMG are discharged and if required scrapping can be performed
5.2.22	Scrapping of the wet mass to be performed if needed to ensure complete discharge of granulated mass.
5.2.23	Close the discharge valve by pressing the ‘stop’ button (red coloured)
5.2.24	For multiple lots of same batch repeat steps 5.2.11 up to 5.2.23
5.2.25	After completion of batch, label the equipment as “To be Type A cleaned” or “To be Type B Cleaned”.
5.2.26	Record the activity in equipment log book as per Annexure.
5.3	Type A Cleaning
5.3.1	Mention on the area status board as “Under Cleaning” prior to initiation of cleaning process.
5.3.2	Ensure that the electrical utilities to the RMG are switched ‘off’ during the cleaning process
5.3.3	Clean the outer surface of the RMG with clean lint free cloth
5.3.4	Remove the adhered powder or granules with the help of Teflon scraper. If required, clean the interior surface of RMG with lint free cloth
5.3.5	Ensure the cleanliness by checking visually for the presence of any granules or particles in the RMG, then affix “Type A Cleaned” label.
5.3.6	Record the activity in equipment log book as per Annexure.
5.4	Type B Cleaning
5.4.1	Mention on the area status board as “Under Cleaning” prior to initiation of cleaning process
5.4.2	Ensure that the electrical utilities to the RMG are switched off during the manual cleaning process
5.4.3	Fill the RMG approx. 2/3rd of capacity with potable water and run the impeller at slow speed and chopper at slow speed for a duration of 15 minutes and flush the washed solution through discharge port
5.4.4	Prepare an approx 0.1% v/v cleaning solution (1 ml of Teepol in 1000 ml of potable water)
5.4.5	Dismantle the impeller and chopper after opening the lock nuts
5.4.6	Scrub the impeller, chopper, interior and exterior surface of RMG with approx 10 liters of washing solution using a nylon scrubber
5.4.7	Flush out the washing solution using approx. 40 liters of potable water
5.4.8	Finally rinse the interior and exterior surface of RMG with approx.50 liters of purified water
5.4.9	Fill the Swab / Rinse Sample Intimation Slip and submit to QA department for collection of samples.
5.4.10	Record the activity in equipment log book.
5.4.11	Collect the Swab/Rinse sample result from QA. If the result is complying, label the equipment as “Type B Cleaned”. If the result is not complying repeat the steps 5.4.3 to 5.4.9.
5.4.12	After successful completion of cleaning process, mention on the area status board as “Type B Cleaned”.
5.5	Breakdown
5.5.1	If breakdown occurs during operation, hold the granules in closed condition. Inform to the Head Production.
5.5.2	Fill the “Complaint Note” and submit to Engineering Department.
5.5.3	Fill the “Incident Report” and submit to Quality Assurance Department.
5.5.4	Unload the granules only if required for breakdown rectification
5.5.5	Store the unloaded granules in suitable SS closed container.
5.5.6	If breakdown occurs prior to start of operation, follow step 5.5.2
5.5.7	Record the breakdown activity in Equipment Log Book.
5.5.8	After completion of repairs, the operations can be resumed. Perform Type A or Type B cleaning if the material has been unloaded from the RMG.
5.5.9	Collect and file a copy of the “Complaint Note” certifying that the repair works have been successfully completed.
5.5.10	Record the repair completion activity in Equipment Log Book.
5.5.11	Describe the breakdown activity in the respective product BMR.
5.6	Preventive Maintenance
5.6.1	Perform the preventive maintenance as per define Annexure.
5.6.2	If preventive maintenance activity is outsourced, the values are to be transcribed in the Annexure, and external party certificate to be attached.
5.6.3	Attach the preventive maintenance label on the equipment
5.7	Calibration
5.7.1	Perform the calibration as per define Annexure .
5.7.2	If calibration activity is outsourced, the values are to be transcribed in the Annexure and external party certificate to be attached

  

6. Abbreviation

Abbreviation	Expansion
TAB	Tablet
RMG	Rapid Mixer Granulator
Kg/cm2	Kilogram
SS	Stainless Steel
LHS	Left Hand Side
RHS	Right Hand Side
BMR	Batch Manufacturing Record
%	Percent
v/v	Volume by volume
FBD	Fluid Bed Dryer
rpm	Rotation Per Minute
ml	Mililitre

 

CALIBRATION OF RAPID MIXER GRANULATOR

ANALOG TIMER

                                      OBSERVATIONS

Sr. No	Reading on UUC In MIN	Reading on Standard instruments HRS:MIN:SEC:MSEC	Deviation ± 2 MIN	Remarks
1	10
2	20
3	40
4	60
5	120
UUC : Unit under calibration

 

PRESSURE GAUGE

OBSERVATIONS

Sr. No.	UUC Reading (Kg/Cm2)	Reading on Standard instruments  (Kg/Cm2)	Deviation   ±0.14 Kg/Cm2	Remarks:
1	0.0
2	1.0
3	2.0
4	4.0
5	6.0
6	7.0
UUC : Unit under calibration
Result: The results Complies / Not Complies with the acceptance criteria.

 

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: Manual Inspection of Tablets and Capsules

1. Objective:

To define procedure for Manual Inspection of Tablets and Capsules.

2. Scope:

This SOP is applicable to manual inspection of tablets and capsules in production department.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedure as mentioned in the SOP.
   • Quality Assurance Department: To give line clearance. To review and approve the SOP.
   • Engineering Department: To perform the Maintenance of the area and providing utility for performing activity.
4. Accountability:

Head, Production Department. Head,  Q.A. Department.

5. Procedure:
   • Definition:
     • Production Associate: Executive or Operator of Production Department or any personnel trained to perform duties as per this SOP.
     • Quality Assurance Associate: Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
     • Engineering Associate: Executive or operator of engineering department trained to perform duties as per this SOP.
     • Type A Cleaning: Dry cleaning with clean lint free cloth in the following cases,
       • Remove the previous batch residue.
       • Before starting the next batch of the same product.
       • Prior to execution of higher strength batches, after the execution of lower strength batches of the same product.
     • Type B Cleaning: Wet cleaning by using soap solution in the following cases
       • Removal of traces of the previous product, and is ensured by testing rinse /swab sample of the cleaned equipment.
       • Change in product/Change in Colour.
       • Prior to execution of lower strength batches, after the execution of higher strength batches of the same product.
       • After continuous five batches of the same product.
       • After seven days of cleaning before use, if equipment is not in use.
       • After replacement or repair of any product contact part or change in colour.
     • Cleaning Solution: 1 ml of Teepol (soap solution) in 1000 ml of potable water (0.1% v/v).
   • Procedure

	Precautions:
5.2.1	Ensure that the line clearance is taken before start of inspection.
5.2.2	Scoops, Containers and Trays used for inspection should be clean.
5.2.3	During inspection, use nose mask and hand gloves.
5.2.4	Ensure that the container used for product storage should be clean and dry.
5.2.5	Ensure that the temperature and relative humidity are within the limit as per product requirement.
5.3	Procedure:
5.3.1	Before starting inspection, check the product container label for   Product Name, Batch No., Net weight, status of the product etc.
5.3.2	After check from production officer, start the inspection of tablets / capsules.
5.3.3	Tablets with defective features like capping, chipping, broken, foreign particles (black particles), other colour spots, laminated, sticking and picking tablets etc. should be removed from the final product.
5.3.4	Defected capsules like double cap, powder on capsule, black or colour spots, printing defects etc should be removed from the final product.
5.3.5	Keep the defected tablets / capsules in separate poly bag with duly labelled as “REJECTS”.
5.3.6	The rejected Tablets / Capsule should be weighed and recorded in Batch Manufacturing Record.
5.3.7	Good sorted tablets / capsules should be weighed and recorded in BMR and transfer to the bulk finished area with proper label.
5.3.8	Rejected tablets / capsules should be disposed off after authorisation from department head and QA.
5.3.9	After completion of activity label the accessories as “To Be Type A Cleaned” or “To Be Type B Cleaned” as per SOP.
5.4	Type A Cleaning (Batch to Batch Cleaning)
5.4.1	Mention on the area status board as “Under Cleaning” prior to initiation of cleaning process.
5.4.2	Remove all previous batch documents, containers and labels from the area.
5.4.3	Clean the trays, Scoops and other accessories with the help of clean dry duster.
5.4.4	Visually ensure the cleanliness and affix “Type A CLEANED” label as per SOP.
5.5	TYPE B Cleaning (Product to Product Cleaning)
5.5.1	Remove in process status label and affix “To be Type B cleaned” status label.
5.5.2	Remove all labels, containers and documents of previous product.
5.5.3	Keep the trays/accessories on trolley and transfer to the wash area for cleaning by covering with poly bag with “To Be Type B Cleaned” label.
5.5.4	Cleaning of Trays/ Accessories: Clean the trays/accessories first with potable water to remove the adhered powder then apply 0.1 % soap (teepol) solution then wash with sufficient quantity of potable water. Finally rinse with purified water.
5.5.5	Fill the Swab / Rinse Sample Intimation Slip and submit to QA department to collect the Swab / Rinse samples of the trays. Refer Annexure.
5.5.6	Collect the Swab/Rinse sample result from QA. If the result is complying, label the equipment as “Type B Cleaned”. If the result is not complying repeat the steps 5.5.4.
5.5.7	Drying of trays: Wipe all Trays/Accessories with a clean dry lint free duster then put the trays in tray cabinet in reverse position.

 

6. Abbreviation:

Abbreviation	Expansion
PDD	Production Department
No.	Number
SOP	Standard Operating Procedure
QA	Quality Assurance
ml	Mili Litre
v/v	Volume by volume

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

 

SOP Title: In-Process Quality Control of Tablets/Capsules

1. Objective:

To define  procedure for in-process checks during production activity.

2. Scope:

This SOP is applicable to in-process quality control checks for tablets and capsules during production activity to assure that the product manufactured is within standard specifications.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedure for in-process checks described in the SOP .
   • Quality Assurance Department: To ensure the products meets the specification. To review and approve the SOP.
   • Engineering Department: To perform the Preventive Maintenance and Calibration of the instruments.
4. Accountability:

Head, Production Department. Head, Q.A. Department.

5. Procedure:
   • Definition:
     • Production Associate: Executive or Operator of Production Department or any personnel trained to perform duties as per this SOP.
     • Quality Assurance Associate: Executive of Quality Assurance Department or any personnel trained to perform duties as per this SOP.
     • Engineering Associate: Executive or operator of engineering department trained to perform duties as per this SOP.
   • Procedure

	Precautions:
5.2.1	Ensure that In-Process Quality Control instruments are cleaned and calibrated before use.
5.2.2	Ensure that the line clearance has been taken prior to starting the batch.
5.2.3	Check that, all the machines and containers should be labelled with the batch identification label.
5.2.5	Use hand gloves while handling the product.
5.2.6	In-process friability checked tablets should not be added in the tablet container. It should be destroyed by putting in water for hazardous waste disposal Bin.
5.3	In-process checks for Tablets:.
5.3.1	Check that the temperature and relative humidity (25oc ± 2oc and 55% ± 5%RH) are within the limit at all stages of manufacturing and packing.
5.3.2	Record the temperature and humidity in individual in-process control sheet of the BMR.
5.3.3	During granulation, in process tests such as LOD should be checked and recorded as mentioned in respective product BMR
5.3.4	Check all the tablets for appearance, embossing (if applicable) and should be free from any physical defects.
5.3.5	Set the compression parameters as mentioned in BMR and collect two rounds of tablets from each discharge chute.
5.3.6	Label the tablet container dully filled with product name, batch number, current stage, next stage, LHS and RHS (if applicable).
5.3.7	In process test samples tested should be counted during reconciliation.
5.3.7	Weigh individual tablets container one by one from LHS as well as RHS and note down the observations in the  product BMR.
5.3.8	In-process sample quantity should be collected as mentioned in individual product BMR.
5.3.9	At the start of compression and thereafter, following in-process tablet parameters should be checked.

 

Sr. No.	In-process Test details	Limits	Frequency
1	Diameter of tablets	As limit mentioned in  BMR	Initially at start of the batch.
2	Group weight of 20 tablets	As limit mentioned in  BMR	Every half an hour.
3	Friability	NMT 1 % w/w or as mentioned in  product BMR	As mentioned in BMR.
4	Thickness	As limit mentioned in  BMR	As mentioned in BMR.
5	Hardness	As limit mentioned in  BMR	As mentioned in BMR
6	Uniformity / individual weight variation	As limit mentioned in  BMR	As mentioned in BMR
7	Disintegration time	As limit mentioned in  BMR	As mentioned in BMR

5.3.10   If the tablets are coated, following in-process parameters have to be checked for coated tablets during coating process as mentioned in BMR.

 

Sr. No.	In-process Test details	Limits	Frequency
1	Inspection of coated tablets for all lots of batch.	Coating   should be uniform, smooth, colour uniformity for whole batch.	As per BMR
2	Group weight of 20 tablets.	As mentioned in product BMR.	As per BMR
3	Thickness of tablets.	As mentioned in product BMR.	As per BMR
4	Hardness of tablets.	As mentioned in product BMR.	As per BMR
5	Disintegration time.	As mentioned in product BMR.	As per BMR

 

5.3.5.3.11	During blister / strip or Bulk packing, in-process checks to be done for cartons, labels and blisters for batch number, date of manufacturing, date of expiry, maximum retail price (if any), other markings and leak test to be performed for blister / strips as mentioned in product BMR.
5.3.12	During blister / strip or Bulk packing, in-process checks to be done for cartons, labels and blisters for batch number, date of manufacturing, date of expiry, maximum retail price (if any), other markings and leak test to be performed for blister / strips as mentioned in product BMR.
5.3.13	Check the over printing matter by referring product specifications or respective product BPR initially and thereafter as frequency mentioned in BPR.
5.3.14	Record the online in process test result in batch packing record.
5.3.15	Collect the number of sample for leak test as mentioned in product BPR.
5.3.16	The entire sample should pass the leak test as per leak test apparatus SOP.
5.3.17	Routinely check the container by visually to ensure that leaflet, silica bag are properly enclosed in containers as per requirement. Ensure the sealing of containers is properly done in case of bulk packing.
5.3.18	Ensure the shrink packing is done properly and check number of cartons or containers in shrink pack whenever applicable.
5.3.19	During bulk packing, check the quantity of tablets packed in the container using manual counter and also check for defective tablets, over printing details of container labels and shipper labels.
5.3.20	During blistering, check the quantity of strips pack in the carton and also check for defective tablets, over printing details of carton and shipper label.
5.3.20	Check the shipper packing and check the pack size of the shipper i.e. number of carton or containers inside the shipper.
5.3.21	Note: If any in-process test fails or difficult to judge the result, then test should be repeated by taking another sample.
5.4	In-process checks for Capsules:
5.4.1	Before start of production activities.
5.4.2	Continuously collect 20 Capsules in SS bowl / poly bag and label accordingly indicating the product name  and Batch No.
5.4.3	Check and record group weight of 20 Capsules as mentioned in the BMR.
5.4.4	Similarly, weigh the individual weight of 20 Capsules one by one and note observations in the BMR or as mentioned in product BMR.
5.4.5	Check the lock length, disintegration test, appearance as per frequency mentioned in respective product BMR.
5.4.6	If required, adjust the machine parameters to comply the test and it should be within specified limit as per BMR.

 

6. Abbreviation:

Abbreviation	Expansion
BMR	Batch Manufacturing Record
BPR	Batch Packing Record
SOP	Standard Operating Procedure
LHS	Left Hand Side
RHS	Right Hand Side
QA	Quality Assurance
LOD	Loss on Drying
oC	Degree Centigrade
%	Percent
w/w	Weight by weight

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.

SOP Title: Operation, and Calibration of Metal Detector

 

1. Objective:

To define procedure for Operation, Cleaning, Preventive Maintenance and Calibration of Metal Detector.

2. Scope:

This SOP is applicable to Metal Detector used for detecting metal particles in final product in Production Department.

 

3. Responsibility:
   • Production Department: To prepare and review the SOP. To follow the procedures laid down for the operation and cleaning and to support for Preventive Maintenance and Calibration of Metal Detector.
   • Engineering Department: To perform preventive maintenance and calibration of Metal Detector.
   • Quality Control Department: To analyse and report the swab/rinse samples.
   • Quality Assurance Department: To provide line clearance prior to operation. To collect the swab/rinse samples. To approve the Preventive Maintenance and Calibration reports. To review and approve the SOP and Annexure.
4. Accountability:

Head, Production Department, Head, Engineering Department and Head Quality Assurance.

5. Procedure:
   • Definition:
     • Production Associate: Executive or Operator of Production Department or any personnel trained to perform duties as per this SOP.
     • Quality Assurance Associate: Executive of Quality Assurance department or any personnel trained to perform duties as per this SOP.
     • Quality Control Associate: Executive of Quality Control department or any personnel trained to perform duties as per this SOP.
     • Engineering Associate: Executive or Operator of Engineering Department trained to perform duties as per this SOP.
     • In-Process Checks: As per the Scope of this SOP the In-Process checks refers to, checking sensitivity of Metal Detector.
     • Non Recoverable Rejects: The Tablets/Capsules which cannot be re processed, for example, Tablets/Capsules rejected during the metal detection Non Recoverable Rejects are to be discarded.
     • Type A Cleaning: Dry cleaning with clean lint free cloth in the following cases,
       • Remove the previous batch residue.
       • During end of the shift.
       • Before starting the next batch of the same product.
       • Prior to execution of higher strength batches, after the execution of lower strength batches of the same product.
     • Type B Cleaning: Wet cleaning by using soap solution in the following cases
       • Removal of traces of the previous product, and is ensured by testing rinse /swab sample of the cleaned equipment.
       • Change in colour.
       • Monthly ,if cleaned equipment not used for production activity.
       • Prior to execution of lower strength batches, after the execution of higher strength batches of the same product.
       • After continuous five batches of the same product.
       • After  cleaning validity before use, if  cleaned equipment is not used for production.
       • After replacement or repair of any product contact part.
     • Cleaning Solution: 1 ml of Teepol (soap solution) in 1000 ml of potable water (0.1% v/v)
     • Breakdown: Any activity leading to operation of machine other than the set parameters and / or unusual sound or vibration observed in the machine
     • Preventive Maintenance: Maintenance activity performed to ensure that the equipment will function smoothly and to avoid breakdowns. These activities are performed monthly, quarterly and half yearly.
     • Calibration: Tests performed to ensure that the equipment is functioning as per set parameters. These test are performed during production as mentioned in product BMR and also after repair or replacement of parts coming in direct contact with product.

 5.2 Procedure:

	Precautions
5.2.1	Ensure that, equipment is cleaned and line clearance is taken as per respective BMR checklist.
5.2.2	Switch ‘OFF’ the main power supply during machine setting, cleaning and product change over activity.
5.2.3	Allow the Metal Detector initially to stabilise at least for 5 minutes.
5.2.4	Metal Detector chute should not be attached to any metal body during operation.
5.2.5	Put “OFF” the mains of Metal Detector during cleaning.
5.2.6	Do not wash inside surface, circuit channel of Metal Detector.
5.2.7	After completion of metal detection, clean the standard metal chips (test samples) with moist cloth then dry with soft clean cloth.
5.3	Operation
5.3.1	Switch “ON” the electrical mains.
5.3.2	Initially Metal Detector LED bar graph will start blinking with opening and closing of flap with glowing green and red colour indicator.
5.3.3	Allow the Metal Detector to stabilize, till the red blinking of bar graph disappears.
5.3.4	After stabilizing Metal Detector, green colour two bulbs will glow and flap will close with green colour “Power ON” indicator glowing.
5.3.5	For sensitivity checking pass the test sample chips of ferrous 0.15 mm, non ferrous 0.25 mm and S.S. 0.25 mm test chips through Metal Detector chute one by one.
5.3.6	During passing all the test chips should deflect (rejects) by opening the rejects flap.
5.3.7	Place the Metal Detector below the outlet chute of de-duster or out let chute of compression machine or capsule filling machine or polishing machine as per the requirement.
5.3.8	Pass the Tablets / Capsules through Metal Detector for detecting metal particles if any, present in the product.
5.3.9	Collect the metal detected Tablets / Capsules in the  clean containers lined with double poly bag. Affix  ‘In Process Label’ to the container as per SOP.
5.3.10	Tablets / Capsules should pass in uniform quantity and should not block the passage or detecting zone.
5.3.11	The Metal Detector channel angle should be maintained as per product shape and size to maintain the uniform flow of Tablets / Capsules by passing the product through Metal Detector.
5.3.12	During operation, Tablets / Capsules should freely pass through the Metal Detector.
5.3.13	Check the Tablets/Capsules ejecting out from the Metal Detector for any defects. Record the rejection details in the product BMR.
5.3.14	At the end of the metal detection or after regular intervals, all the deflected Tablets / Capsules should be removed from the rejection collection box and should be re- passed through the Metal Detector.
5.3.15	The finally rejected Tablets / Capsule should be labelled as  ‘Non Recoverable Rejects’.
5.3.16	Weigh the metal detected Tablets/Capsules and rejected Tablets/Capsules for yield reconciliation. Record the respective weight in the BMR
5.3.17	These rejections should be destroyed after proper authorisation from Production Head and QA.
5.3.18	If any metal contaminated Tablets / Capsules  rejection observed during compression / capsule filling, then stop the  compression / capsule filling activity and check the metal source of the machine or friction of any metal part.
5.3.19	After rectification, start the regular production activity.
5.3.20	Standard limits: Metal particles should be absent in final product.
5.3.21	At the end of operation, check the sensitivity of Metal Detector. If any discrepancy is observed, re-pass all the previously checked Tablets / Capsules through the Metal Detector.
5.3.22	After completion of metal detection, switch “OFF” the Metal Detector.
5.3.23	Clean the test chips and store them in the container provided.
5.3.24	After completion of metal detection activity, label the equipment as “To be Type A cleaned” or “To be Type B Cleaned” depending on use.
5.3.25	Record the activity in equipment log book as per Annexure.
5.4	Type A Cleaning
5.4.1	Mention on the area status board as “Under Cleaning” prior to initiation of cleaning process..
5.4.2	Ensure that the electrical utilities to the Metal Detector are switched ‘OFF’ during the cleaning process.
5.4.3	Dry clean the equipment with the help of Vacuum Cleaner or clean dry duster to remove the powder.
5.4.4	Remove acrylic cover and wipe with clean dry duster.
5.4.5	Dry clean the rejects collection box with dry clean duster.
5.4.6	Ensure the cleanliness by checking visually for the presence of previous batch  particles, then affix “Type A Cleaned” label.
5.4.7	Record the activity in equipment log book as per Annexure .
5.5	Type B Cleaning
5.5.1	Mention on the area status board as “Under Cleaning” prior to initiation of cleaning process.
5.5.2	Ensure that the electrical utilities to the Metal Detector are switched ‘OFF’ during the cleaning process.
5.5.3	Dry clean the Metal Detector with the help of Vacuum Cleaner or clean dry duster to remove the powder.
5.5.4	Remove the Teflon Chute by pulling back and dismantle acrylic cover, dismantle the S.S. inlet chute by removing the hexagonal bolt then transfer these parts to the wash area by covering in poly bag with “To be Type B Cleaned” label.
5.5.5	Wash the above parts with 0.1 % soap solution (teepol) prepared as per the SOP preparation of cleaning agent solution. Then wash with sufficient quantity potable water, finally rinse with purified water.
5.5.6	Disconnect terminals of solenoid valve and disconnect the reject flap assembly and wipe its surface with soft clean moist cloth dipped in purified water then wipe with clean dry duster.
5.5.7	After assuring cleanliness, dry the above parts with a clean dry lint free duster /   compressed air.
5.5.8	Assemble the dismantled parts in its place properly and label the equipment as “ Type B Cleaned”.
5.5.9	Fill the Swab / Rinse Sample Intimation Slip and submit to QA Department for collection of samples.
5.5.10	Record the activity in equipment log book as per Annexure.
5.5.11	Collect the Swab/Rinse sample result from Quality Assurance Department. If the result is complying, label the equipment as “Type B Cleaned”. If the result is not complying repeat the steps 5.5.5 to 5.5.6
5.5.12	After successful completion of cleaning process, mention on the area status board as “Type B Cleaned”.
5.6	Breakdown
5.6.1	If breakdown occurs during operation, hold the dedusting and metal detection process. Inform to the Head Production.
5.6.2	Fill the “Complaint Note” and submit to Engineering Department.
5.6.3	Fill the “Incident Report” and submit to Quality Assurance Department.
5.6.4	Unload the product only, if required for breakdown rectification.
5.6.5	Store the unloaded tablets/ capsules in suitable closed container
5.6.6	If breakdown occurs prior to start of operation, follow step 5.6.2
5.6.7	Record the breakdown activity in Equipment Log Book.
5.6.8	After completion of repairs, the operations can be resumed. Perform “Type A or Type B” cleaning if the material has been unloaded from the machine.
5.6.9	Collect and file a copy of the “Complaint Note” certifying that the repair works have been successfully completed.
5.6.10	Record the repair completion activity in Equipment Log Book. Refer Annexure.
5.6.11	Describe the breakdown activity in the respective product BMR.
5.7	Preventive Maintenance
5.7.1	Perform the Preventive Maintenance as per Annexure.
5.7.2	If Preventive Maintenance activity is outsourced, the values are to be transcribed in the Annexure and external party certificate to be attached.
5.7.3	Attach the Preventive Maintenance label on the equipment.
5.8	Calibration / Sensitivity Checking:
5.8.1	Sensitivity Checking: For sensitivity checking, pass the test chips of ferrous 0.15 mm,   non ferrous 0.25 mm and S.S. 0.25 mm through metal detector chute one by one. All the test chips should get rejected by opening the reject flap.
5.8.2	Frequency for Sensitivity Checking: 1. At the start and end of operation, in-between at regular intervals as mentioned in  Batch Manufacturing Record. 2. After every switch “ON” or after resuming power.

 

6. Abbreviation :

Abbreviation	Expansion
SOP	Standard Operating Procedure
PD	Production Department
TAB	Tablet
S.S.	Stainless Steel
CAP	Capsules
mm	Millimetre
BMR	Batch Manufacturing Record
QA	Quality Assurance
%	Percent
v/v	Volume by Volume
ml	Mili Litre
LED	Light Emitting Diode

 

*Note – Ready to use SOP available in “DOWNLOAD” Section.