SOPs

Purpose :

The purpose of this SOP is to describe the setting, operation and cleaning procedure of Rapid Mixer Granulator Machine (Model: M-150) in order to comply with cGMP standard.

Scope :

The scope of the procedure is applicable to the Rapid Mixer Granulator Machine (Model: M-150) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

PLC : Programmable Logic Controller
CIP : Clean In Place

Responsibilities:

The roles and responsibilities are as follows:

Operator

Operation and cleaning of the Rapid Mixer Granulator Machine (Model: M-150).
Maintaining Equipment Log Book.

Executive, Production

To monitor and check the laid down procedure.

Manager, Production

To implement this correctly.

Manager, Quality Assurance

To approve the Document.

Vibratory Sifter, Purpose :

Vibratory Sifter, The purpose of this SOP is to describe the setting, operation and cleaning procedure of Vibratory Sifter Machine (Model: BT-800-3S) in order to comply with cGMP standard.

Vibratory Sifter, Scope :

The scope of the procedure is applicable to the Vibratory Sifter Machine (Model: BT-800-3S) at the Production area of General block of Labaid Pharmaceuticals Limited.

Definitions / Abbreviation:

N/A.

Responsibilities:

The Roles and Responsibilities are as follows:

Operator

Operation and cleaning of the Vibratory Sifter Machine (Model: BT-800-3S)
Maintaining Equipment Log Book

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 :

[][]Make sure that the power cable is separated from the socket before and after operation.
[][]The sifter covers and lid are in lock position during operation.
[][]Use face mask, rubber gloves and protective clothing during handling of materials.
[][]Check the cleanliness of sifter, sieves and gasket before assembling of machine.
[][]Check the sieve for its integrity before and after completion of operation.

Machine Assembling

[][]Keep the necessary change parts near the sifter machine before assembling.
[][]Assemble the sifter by putting cover with discharge opening on top of body of sifter.
[][]Then set the clamp to tighten the cover.
[][]Then place required sieve.
[][]On the top of first cover set the second cover with discharge opening.
[][]Set the clamp to tighten the second cover.
[][]Place the required sieve.
[][]Set the third cover with discharge opening.
[][]Set the clamp.
[][]Set the lid cover of sifter.
[][]Set the clamp.

Machine Operation

[][]Connect the power cable to the socket for power supply.
[][]Switch on the machine by pressing green button on the lower part of the machine.
[][]Input the material through the lid opening.
[][]Sieve the material and collect sieved material through the cover discharge opening.
[][]After operation switch off the sifter machine by pressing red button on the lower part of machine.
[][]Record the machine operation parameters in the ‘Equipment Log Book’

Machine Dismantling

[][]Remove the clamp of lid cover.
[][]Remove the lid cover.
[][]Remove the clamp of third cover.
[][]Remove the third cover.
[][]Remove the clamp of second cover.
[][]Remove the second cover.
[][]Remove the sieve.
[][]Remove the clamp of first cover.
[][]Remove the cover.
[][]Remove the sieve.

Machine Cleaning

[][]Remove dusts from the machine body and other necessary parts with a vacuum cleaner.
[][]Clean all the machine parts with dry lint free cloth.
[][]Use potable water to clean the machine body, product contact parts, clamps and other machine parts.
[][]Use hot water to clean all the product contact parts.
[][]Finally rinse the machine body, product contact parts, clamps and other machine parts with purified water.
[][]Remove the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Dispensing Booth, Purpose :

Dispensing Booth, The purpose of this SOP is to describe the operation and cleaning procedure of Dispensing Booth (Model: Standard) in order to comply with cGMP standard.

Dispensing Booth, Scope :

The scope of the procedure is applicable to the Dispensing Booth (Model: Standard) at the Production area of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A.

Responsibilities:

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

Operator

[][]Operation and cleaning of the Dispensing Booth (Model: Standard)
[][]Maintaining Equipment Log Book

Executive, Production

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

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Annexure:

[][]N/A.

Procedure

Precautions:

[][]The working person must follow safety procedures of works.
[][]For any trouble, disturbance switch OFF the Dispensing Booth.

Machine Operation

[][]Check the machine first physically.
[][]Check electric connection and mechanical set up.
[][]Machine switch on.
[][]Light on and blower on.
[][]Open the door.
[][]After completion desired work clean the Laminar Unit properly.
[][]Close the door and switch off main switch.
[][]Switch ON Dispensing Booth.
[][]Switch ON Light.
[][]Switch ON the Laminar Air Flow.
[][]Increase or decrease air flow by pressing up/down button.
[][]Warm up the Dispensing Booth for 30 minutes before starting dispensing.
[][]Record the machine operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Cleaning

[][]Remove dusts from the dispensing booth with a vacuum cleaner and then clean with lint free cloth.
[][]Use wet cloth to clean the booth.
[][]Wipe the water with lint free cloth.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters in the ‘Equipment Log Book’

Dust Collector , Purpose:

Dust Collector , The purpose of this SOP is to describe the setting, operation and cleaning procedure of Dust Collector in order to comply with cGMP standard.

Dust Collector , Scope:

The scope of the procedure is applicable to the Dust Collector at the Production area of of XX Pharmaceuticals Limited.

Definitions / Abbreviation:

[][]N/A

Responsibilities:

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

Operator

[][]Setting, operation and cleaning of the it
[][]Maintaining Equipment Log Book

Executive, Production

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

Manager, Production

[][]To implement this correctly

Manager, Quality Assurance

[][]To approve the Document

Procedure:

[][]Machine Assembling
[][]Open dust collectors lid.
[][]Set the filter bag inside the Machine.
[][]Set the upper lid cover of the Machine.
[][]Connect the dust collecting hose pipe.

Machine Operation

[][]Connect electrical cable of it.
[][]Connect ithose pipe with Tablet Compression Machine.
[][]Switch ON the main power of it from the PLC of the compression machine.
[][]Record the operation start time & end time and other parameters on the ‘Equipment Log Book’

Machine Dismantling

[][]Switch OFF the compression Machine.
[][]Remove electrical connection.
[][]Remove dust collecting hose pipe from compression Machine.
[][]Remove the upper lid of the it.
[][]Remove the filter bag.

Machine Cleaning :

[][]Remove dusts from the machine with a duster.
[][]Use potable water to clean the machine body and filter bag.
[][]Finally clean with purified water.
[][]Clean and swab with lint free cloth all the parts and the machine body to dry any water.
[][]After final cleaning affix the ‘CLEANED’ label.
[][]Record the cleaning parameters on the ‘Equipment Log Book’

Annexure:

Annexure I Equipment Use Log Book

Water Handling System, Purpose:

Water Handling System, To lay down the procedure of Water handling system at the Production premises.

Water Handling System, Scope:

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

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 laid down procedure.

Manager, Production

[][]To implement this correctly.

Head of Quality Assurance

[][]To approve the Document.

Annexure:

[][]N/A

Procedure:

Precaution :

[][]During collection of hot water, wear heat resistance gloves.
[][]Before collection check all the point of connection & ensure that no one is open.
[][]Keep all inlet and outlet of circulating loop / storage tank and open ends of S.S. pipelines closed at the day end of work
[][]Always keep the water off-take valves closed at every use point after use.
[][]At the end of the day, ensure that no flexible hose pipe remains attached with the use point.
[][]Potable water should not be use in manufacturing process.

Types :

[][]Three types of water used in Manufacturing area.
Potable Water
Hot Water
Purified Water
Potable Water
[][]Connect pipe with the potable water system.
[][]Check availability of potable water in the line.
[][]Collect potable water from potable water mark water line.
[][]Use Pharma grade container to collect potable water for cleaning purpose.
[][]Transfer potable water to the respective production area by using SS trolley.
[][]After completion of work hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work.

Hot Water

[][]Connect pipe with the hot water system.
[][]Check availability of hot water in the line.
[][]Collect hot water from hot water mark water line.
[][]Use Pharma grade container to collect hot water for cleaning purpose.
[][]Transfer hot water to the respective production area by using SS trolley.

Purified Water

[][]Before Collection of purified water from the main re-circulation loop of purified water, connect the pipe with 50 Liter storage tank and main loop.
[][]Collect the purified water into the storage tank by turning the valve open.
[][]Circulate the water through the sectional circulation loop for 5 minutes and drain through use points and storage tank outlet.
[][]Transfer purified water to the respective production area by using SS trolley.
[][]After completion of work, disconnect the pipe between the pipe storage tank and main circulating loop and hang the pipe on the hanger.
[][]Keep both ends close with Alu foil after drain out of remaining water from pipe at the end of the day work

Rework Residue , Purpose:

Rework Residue , To lay down a procedure for Handling of Rework Residues from Batch Processed Material /Intermediate product.

Rework Residue , Scope:

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

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 laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Do not add any rework unless it is authorized beforehand by Head of Quality Assurance.
[][]Do not add the rework of a batch to other batch (es) until packing of the batch is completed.
[][]Ensure that rework of different products is not stored in the same container.
[][]Do not store any rework which is less than 0.25 % of the actual batch size.

Rework Residue :

[][]Following stated defects can be considered for storage and addition as rework in a batch leftover granules, chipping / capping defects, lamination, tablets with variations in physical parameters like weight, hardness, thickness, friability or edge broken tablets at the time of compression, coating and inspection. Residue after compression, encapsulation & PFS is also be considered as rework.
[][]Prepare a ‘Rework Residue Addition Note’ as per format (Annexure-I). The rework addition note shall be approved beforehand by Head of Production or his designate and authorized by Head of Quality Assurance.

[][]Process the rework as per Batch Manufacturing Record (BMR) of the specific product from the declared necessary step(s).
[][]Maximum allowable amount for addition of rework in a fresh batch is 5 % of actual batch size.
[][]Rework bulk shall be free from any foreign matter, objectionable color and / or odor.
[][]First batch of any product in which rework is added shall be kept for stability study.

Non-Rework :

[][]Any amount of tablets / capsule(s) which is collected as ‘Rework’ but is less than 0.25 % of the actual batch size shall be considered as ‘non-rework’.
[][]‘Non-rework’ shall be destroyed as per Quality Assurance SOP.

Storage of Rework :

[][]Store the rework in tightly closed double lined polybag with “REWORK’ Label in a container on a pallet in WIP Tablet/Capsule store.
[][]Rework of more than one batch of the same product can be stored in one container with proper status label.
[][]Record the rework generated from the batch(es) and their addition history in ‘Rework Residue
[][]Register’ as per (Annexure II). The register shall be kept in production Executive.
[][]Issue rework residues for use only in the presence of Production Executive.
[][]Rework generated from a batch shall be added to the batch(es) which are manufactured within the next three months. For example, rework generated from a batch manufactured in January shall be added to only the fresh batch manufactured within April, not to be added to the batch manufactured in May and so on. But in that case expiry of the fresh batch where rework is added shall be same as expiry of rework batch. In such cases rework shall not be stored for more than 90 days. If any rework amount is left after the said period, destroy the left over with prior approval of Quality Assurance (QA).

Annexure:

Annexure I – Rework Reside Addition Note.
Annexure II – Rework Residue Register.

Additional Materials Return procedure, Purpose:

Additional Materials Return procedure, To lay down the procedure for return of Additional Part of Raw (Excipient) and Primary Packaging materials to Ware-House.

Additional Materials Return procedure, Scope:

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

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 laid down procedure.

Manager, Production

[][]To implement this correctly.

Manager, Quality Assurance

[][]To approve the Document.

Procedure:

Precaution:

[][]Ensure weighing and counting of the materials is correct.
[][]Returning of Unused Raw Materials (Excipient)
[][]After dispensing unused Raw Material (Excipient) can return to store.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.
[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and third copy shall retain in the book as reference copy.

[][]Returning of Unused Primary Packaging Materials
[][]After dispensing unused Primary Packaging Material can return to store.
[][]Individual rolls of Aluminum foil, PVDC and Alu bottom film which is return shall weigh and glass bottle, stopper and Alu cap shall count.
[][]Enter all the details like Product Name, Batch No., Batch size, Name of the material, Quantity to be returned, Material ID No., Lab. Control No. on the ‘Stock Return Note’ (Annexure – I).
[][]Operator shall mention all details in Stock Return Note (SRN) and Executive, Production shall check all of them accordingly.

[][]The SRN shall have triplicate copy. All the copies shall be moved along with the physical stock to the Ware-House and Executive / In-charge, Ware-House shall return the rest 02 (Two) copies to the Packaging after duly signed. One copy shall attach with Batch Manufacturing Record and another copy shall retain in the book as reference copy.

Returning of Raw Materials (Excipient) / Primary Packaging Materials Rejecting Online

[][]When the raw materials (excipient) / primary packaging materials are observe to be defective on-line such as having lumps or foreign materials in case of raw materials (excipient) and sealing problem or pinholes in case of foils keep aside the material.
[][]On line rejected material shall return to warehouse as per handling of on line rejection guideline of QA.

Annexure:

Annexure I – Stock Return Note.

Machine Handling, Purpose :

Machine Handling, To lay down the procedure for handling of machine during breakdown.

Machine Handling, 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:

Precaution :

[][]Ensure that proper safety instructions are followed.

Activities:

[][]Shut OFF the main switch of the electric connection.
[][]Inform working Exe. / Sr. Exe., Production about the break-down status of the machine and In-charge is needed to confirm the extent of break-down priority basis.
[][]After checking the nature of break-down, he will intimate Engineering department through ‘Maintenance Request Form’ ( Annexure – I ) Send it to the General Manager, Engineering or his nominee for immediate course of action.
[][]Put off others utility line immediately one by one, so that, the machine turns neutral.
[][]Collect all the processing materials / intermediates and also product into the air-tight container being available before break-down of the machine.
[][]Clean the machine surface and outside by the vacuum cleaner and also the lint free cloth.
[][]Display the label ‘Under Maintenance’ on the front side of the machine for declaring its status.
[][]Involve machine Operator(s) throughout the Maintenance Process for speed up the Engineering job.
[][]Record the total down time of the Machine in the ‘Equipment Log Book along with it’s cleaning for next processing.
[][]Inform Quality Compliance Personnel to verify the extent of machine cleaning for next processing.

Annexure:

Annexure I – Maintenance Request Form 

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.