Manufacture of Liquids, Creams and Ointments

Principle
Liquids, creams and ointments may be particularly susceptible to microbial and other
contamination during manufacture. Therefore special measures must be taken to prevent any contamination.


Premises and equipment

  1. The use of closed systems for processing and transfer is recommended in order to protect the product from contamination. Production areas where the products or open clean containers are exposed should normally be effectively ventilated with filtered air.
  2. Tanks, containers, pipework and pumps should be designed and installed so that they may be readily cleaned and if necessary sanitised. In particular, equipment design should include a minimum of dead-legs or sites where residues can accumulate and promote microbial proliferation.
  3. The use of glass apparatus should be avoided wherever possible. High quality stainless steel is often the material of choice for parts coming into contact with product.
    Production
  4. The chemical and microbiological quality of water used in production should be specified and monitored. Care should be taken in the maintenance of water systems in order to avoid the risk of microbial proliferation. After any chemical sanitisation of the water systems, a validated flushing procedure should be followed to ensure that the sanitising agent has been effectively removed.
  5. The quality of materials received in bulk tankers should be checked before they are
    transferred to bulk storage tanks.
  6. Care should be taken when transferring materials via pipelines to ensure that they are delivered to their correct destination.
  7. Materials likely to shed fibres or other contaminants, like cardboard or wooden pallets, should not enter the areas where products or clean containers are exposed.
  8. Care should be taken to maintain the homogeneity of mixtures, suspensions, etc. during filling. Mixing and filling processes should be validated. Special care should be taken at the beginning of a filling process, after stoppages and at the end of the process to ensure that homogeneity is maintained.
  9. When the finished product is not immediately packaged, the maximum period of storage and the storage conditions should be specified and adhered to.

SOP For Operation and Cleaning Of Compression Machine

Standard Operating Procedure (SOP) for Cleaning and Operation Procedure for double rotary Tablet Compression Machine (45 And 55 Station).

Operation and Cleaning Procedure of Tablet Compression Machine

PURPOSE:

  • To lay down the efficient cleaning and operation of Double rotary compression machine Cadpress 45/55 stations Mark IV.

SCOPE:

  • This procedure is applicable for the cleaning and operation of Double rotary compression machine Cadpress 45/55 stations Mark IV.

 REFERENCES:

  • Equipment Manual
  • SOP for Identification and Status Labelling Procedure.

 DEFINITION:

  • Cleaning:
  • The removal of the residual product or extraneous matter including microbial contamination from the facility surfaces and/or equipment to an acceptable level and maintaining the condition of the facility or equipment such that it can be used safely for subsequent use.
  • Clean-In-Place:
  • A process using a cleaning agent in a pumping system that circulates the solutions through process lines or process equipment in order to clean them without relocation or disassembly.
  • CIP cleaning may be performed using a fully automatic stand-alone cleaning system, or maybe performed by a manually controlled cleaning process where the washing/rinsing steps are initiated by manual manipulation of the various valves.
  • Cleaning Tool:
  • The tool most commonly used for the removal of soils and the application of disinfectants or sanitizers to floors, walls, etc.
  • Tools must be either disposable or capable of being easily cleaned to render them microbiologically sanitary between uses.
  • Equipment:
  • A device that operates either as a “standalone” or combines several instruments or pieces of equipment to give an output. The equipment performs a unit operation or many unit operations.
  • Obtained by distillation, reverse osmosis, or ion exchange. Purified water is prepared from water complying with regulations for drinking water.
  • It must meet compendial tests for chemical and microbiological purity.

PROCEDURE – SOP FOR COMPRESSION MACHINE:

  • Checks and Precautions – Compression Machine:
  • Ensure that die locking screws are not loose it may lead to accident.
  • Ensure that punches are freely moving in the dies and cam tracks.
  • Set the force feeder/ feed frame of the compression machine in such a manner to avoid friction with the turret.
  • Wear the secondary over gowning before starting the operation.
  • Do not clean the compression machine in the running condition.
  • Do not leave any granules in the hopper in case of a stoppage of the compression machine for the undue period and at the shift end.
  • Cleaning Procedure of Compression Machine:
  • For Product to Product Changeover:
  • Switch OFF the main electric supply to the compression machine.
  • First, check the emptiness of hooper and filling the chute.
  • Remove Under Process labels from the compression machine, and respective areas and fix ‘TBC’ labels on them.
  • Disconnect the hopper transfer it to change part trolley. Transfer to the washing area.
  • Clean the hopper with 2 % nonionic detergent solution, followed by potable water.
  • Finally, wash with purified water, and then dry it using compressed air or clean dry lint-free duster.
  • Release hydraulic pressure on the pressure rollers.
  • Collect and label the non-recoverable powder and tablets from the compression machine and destroy it as per the SOP of handling and destruction of Non-recoverable recovery.
  • Record the quantity of non-recovery in the BMR.
  • Collect and label the recoverable powder/tablets from the compression machine and handled as per SOP of ‘Handling and use of residual recovery”.
  • Dismantle and remove hopper, force feeder, scrapper plate, acrylic parts, lower cam guards, discharge chutes, parts of the dedusting machine, and transfer to change part trolley duly labeled with ‘TBC label’.
  • Transfer this change part trolley to the washing area.
  • Wash all the parts using 2% non-ionic detergent followed by potable water and finally rinse with purified water.
  • Dry the parts with a clean dry lint-free cloth or with compressed air or with hot air.
  • Remove leftover powder from the compression machine using dry cloth/blower/compressed air.
  • Remove dust cup respective upper punch one by one and clean each punch along with dust cup with IPA soaked cloth followed by dry lint-free cloth and put them horizontally on die-punch handling tray duly labeled with details of punch specifications and their quantities.
  • Take out all the lower punches one by one by rotating the turret manually and clean each punch with IPA soaked cloth followed by dry lint-free cloth. Put the punches on the die-punch handling tray in a horizontal position.
  • Unscrew the die locks and remove all the dies one by one with the help of die bar. Put the dies on the die-punch handling tray after cleaning them with IPA followed by dry lint-free cloth.
  • Transfer this die-punch handling tray to the tool room. Lubricate the punches with liquid paraffin and store them in the respective die-punch storage cabinet.
  • In case the same punch set is to be used for the next product, clean the punches and dies with IPA, wipe out the IPA with a dry cloth.
  • Clean the upper punch and lower punch guide holes and die holes thoroughly with IPA using a bottle brush. Clean the cam tracks and turret with IPA using a lint-free cloth.
  • Finally, wipe with a clean dry lint-free cloth.
  • Clean all the exposed parts of the compression machine excluding the PLC screen with IPA wet cloth followed by a dry cloth.
  • Wipe analytical balance, the container of mask and gloves, tablet inspection plate, and trolley with IPA soaked cloth followed by a clean dry cloth.
  • After QA approval remove the label from the compression machine, area, and affix ‘Cleaned’ label.
  • Record the cleaning of the compression machine in a sequential log and equipment cleaning record and take QA approval for cleaning.
  • After QA approval remove ‘Cleaned’ label and affix in BMR, which is to be counter checked by QA.

Note: The cleaning of the equipment remains valid for 48 hours for the product to product cleaning. If the equipment is not used within 48 hours, then it should be re-cleaned as per above procedure before use.

  • For batch to batch changeover:
  • Switch OFF the main electric supply to the compression machine.
  • First, check the hopper emptiness
  • Fix ‘TBC’ label on the compression machine and respective areas a
  • Release hydraulic pressure on the pressure rollers.
  • Collect and label the non-recoverable powder tablets from the compression machine and destroy it as per the SOP of handling and destruction of Non-recoverable recovery.
  • Record the quantity of non-recovery in the BMR.
  • Collect and label the recoverable powder/tablets from the compression machine and handled as per SOP of ‘Handling and use of residual recovery”.
  • Ensure that no compressed tablet remains in the dedusting unit.
  • Remove the force feeder.
  • Clean upper punches one by one along with a dust cap.
  • Remove any excess powder from the turret and the compression machine using blower or by dry cloth or with compressed air.
  • Affix ‘Partially Cleaned’ card on the compression machine, area, and take QA approval for cleaning.
  • Record the cleaning in the Equipment Sequential Log.
  • After QA approval remove ‘Partially Cleaned’ card and fix it in the BMR and then affix the ‘Area/Equipment’ status label which is to be counter checked by QA.

Note: The cleaning of the equipment remains valid for 48 hours for batch to batch cleaning. If the equipment is not used within 48 hours, then it should be re-cleaned as per procedure for product to product changeover before use.

  • Change Part Trolley Cleaning Procedure during product to product changeovers:
  • After cleaning of all desalted parts, clean the change part trolley with 2% non-ionic detergent, then with potable water and finally rinse it with purified water.
  • Dry the change part trolley with a dry lint-free cloth or with compressed air or with hot air
  • Then transfer the cleaned part to it and close the doors and transfer it to compression cubicle.

Note: The cleaning of the equipment remains valid for 48 hours for the product to product cleaning. If the equipment is not used within the 48 hours, then it should be re-cleaned as per the procedure of product to product changeover before use.

  • After maintenance of Compression Machine:
  • If the product part is repaired then clean the compression machine as per the procedure laid down for Product Change Over.
  • In case any welding is done on the product contact parts clean as per SOP of cleaning of newly received SS fabricated parts/equipment/ machines.
  • For maintenance of non-contact parts clean the compression machine to be free of oil,grease marks and ensure to cover the machine with the plastic sheet.
  • Assemble the Compression Machine as below:
  • Take out and check the required punches as per the BMR from the punch storage cabinets.
  • Clean die and punches with IPA soaked cloth and finally with the dry lint-free cloth.
  • Fix all the dies on the turret one by one.
  • In case of other than round shape punches, the die should be positioned with the help of upper punches.
  • Lock the dies tightly.
  • Do not use any pipe or spanner for tightening the die locks.
  • Use only Allen keys.
  • Insert lower punches one by one through the lower punch loading hole.
  • Ensure that the lower punches go in the die smoothly.
  • Once all the lower punches are inserted and Insert the brake plugs and fix the anti turning springs over it to hold the lower punches and lock it.
  • Fix the scrapper plate keeping minimum clearance to avoid powder leakage below it and also to avoid its friction with the turret.
  • Now adjust the granules recirculating band with scrapper blade.
  • Insert the upper punches in the upper punch holes and ensure the smooth movement. (In case of other than round shape punches, upper punches inserted along with the dies).
  • Fix all the lower guards.
  • Fix discharge chute assembly.
  • Assemble force feeder and fix it on the compression machine.
  • Fix the hoppers over the force feeder.
  • Rotate the compression machine manually and ensure the free movement.
  • Attach the cleaned dedusting unit with the compression machine.
  • Operating Procedure of Compression Machine:
  • Setting & operating the compression machine after the changeover:
  • Ensure that the AHU and dust collector is ON.
  • Check the temperature and %RH of the cubicle and record.
  • Fix the lubricated granules in hopper after verifying the label of the IPC as per the BMR and counter checking the weight of the IPC with respect to BMR, and fix it with t flow the granules in the hopper.
  • Then feed the granules in hopper manually, in case of lubricated granules store in IPC, and open the hopper valves to feed the feeders.
  • Switch ON the mains of the compression machine and switch on the main motor of the machine.
  • Enter the password in PLC to operate the compression Machine.
  • Apply the hydraulic pressure on Cadpress 45/55 as per BMR or as per Annexure-1.
  • In manual mode of feeder, feed the granules in the feeders.
  • Once the force feeder are filled with the granules change from manual mode of feeder to auto mode and start the compression machine by pressing the switch for few seconds and again stop the machine by stop switch.
  • Discard the initial 2 rounds tablets as non-recovery.
  • Place appropriately labeled double polyethylene lined clean HDPE containers at the outlet of the dedusting machine to collect the tablet.
  • In case the dedusting machine is not used, collect the tablets in the perforated SS bowl.
  • After the bowl is filled with the tablets, dedust the tablets manually and transfer the dedusted tablets in to appropriately label double polyethylene lined clean HDPE containers.
  • Again start the compression machine and collect a few tablets from the both sides.
  • Check these tablets for weight and thickness.
  • Accordingly set the weight hardness and thickness with the help of weight dozer and pressure wheel respectively.
  • Repeat the above step till the correct desired weight, hardness, and thickness achieved.
  • Once the weight, thickness, and hardness of the tablets are set, check the physical appearance & other parameters as per BMR.
  • Adjust all the parameters as per requirement in the BMR.
  • Keep all the above tablets in a separate bag and label as recovery.
  • Once all the parameters are set properly, then take approval from QA for setting parameters.
  • After QA approval starts the machine.
  • In case, the dedusting machine is attached to the machine. start dedusting machines and then start the compression machine.
  • During the end run of the batch, crush the recovery collected during the operation in clit mill through a suitable screen size and mix it with approx.
  • Double quantity of the fresh granules in a polybag and then compress those to tablets.

                 Note: Do not run the compression machine without powder in the feed frame/force feeder.

  • Stoppage of Compression Machine during breaks:
  • Switch ‘Off ‘the machine and dedusting machines (In case in use ).
  • Switch ‘Off’ the machine mains.
  • Close the containers of the granules and tablets with lids.
  • Switch ‘Off’ the lights of the cubicle.
  • Stoppage of Compression Machine at the end of the shift:
  • Switch ‘Off’ the machine and dedusting machines (In case in use).
  • Switch ‘Off’ the mains and disengage from the socket, if required.
  • Remove the granules from the hopper, turret/feeders, and keep them in granules container in case of hygroscopic/corrosive products.
  • Clean the machine externally with dry duster/vacuum cleaner.
  • Switch ‘Off’ the lights of the cubicle.
  • Switch ‘Off’ all electrical connections of the cubicle.
  • Close the valve of the hopper.
  • A restart of Compression Machine after the break:
  • Switch ‘On’ the lights of the cubicle.
  • Switch ‘On’ the main power supply to the machine.
  • If used, Switch ‘On’ the dedusting machines.
  • Start the compression after checking the Tablet Avg. weight.
  • At the end of the completion of the batch:
  • Switch ‘Off’ the machine.
  • Switch ‘Off ’ the dedusting unit.
  • Remove all the tablets from the dedusting machine.
  • Collect tablets in suitably labeled polybag lined containers.
  • Collect and label the non-recoverable powder and tablets from the machine and destroy it as per the SOP of handling and destruction of Non-recoverable recovery.
  • Record the quantity of non-recovery in the BMR.
  • Collect the recovery from the force feeder, turret, and dedusting machine.
  • Label the recovery and store it in the recovery room. Record the qty. of recovery in the BMR.
  • Remove all the filled & empty containers from the cubicle.
  • Weigh each and every container and record it in the BMR.
  • Transfer empty containers in the washing area for washing.

SOP for Sampling of Packing Material

Standard Operating Procedure (SOP) for the sampling of packing material (Primary Packing Material, Secondary Packing Material, and Tertiary Packing Material).

Procedure for Sampling and AQL of Packing Material

PURPOSE:

  • The purpose of this SOP is to define the procedure for sampling and acceptance Quality level of packing materials.

SCOPE:

  • This SOP is applicable for sampling and acceptance Quality level of all primary, secondary and tertiary packing materials at the quality control department of the pharmaceutical drug manufacturing plant.

DEFINITION- SOP FOR SAMPLING OF PACKING MATERIAL:

  • Primary Packing Material: The Packing Material, which is in direct contact with product for e.g: Foil, PVC, PVDC, bottles, etc.
  • Secondary Packing Material: The Packing Material which contains primary unit pack or pack-insert for e.g Show box, Package inserts, etc.
  • Tertiary Packing Material: The Packing Material, in which secondary unit pack contained is tertiary
  • packing material e;g corrugated box etc.

7.0   PROCEDURE FOR SAMPLING OF PACKING MATERIAL:

  • Sampling of Packing Materials:
  • On receipt GIM from Packing material stores, QC section head or designee makes an entry in the in packing material inward register.
  • QC officer shall ensure that stores have affixed the “Quarantine” labels on all the containers/boxes/rolls of packaging material received under a consignment,
  • Excluding corrugated box, where affix the quarantine labels on bundles wise is required and verify the materials against the GIM for quantity, no. of rolls/packs, conditions of the consignment.
  • Use gloves and nose masks during sampling of packing material(where required).
  • At the time of show box sampling, check for each multi up’s sheet.
  • Sampling shall be done by A.R. No., Sampling of two or more A.R. No. should not be done simultaneously.
  • Necessary care to be taken to prevent mix up of the different types of material during sampling.
  • Check the following identity during sampling of the consignment like name of the material, name of the manufacturer, qty. received, the total number of rolls & compare with the GIM.
  • Also, ensure that the supplier status label shall be affixed on all the containers/boxes/rolls by the supplier.
  • Collect the samples randomly by opening different packs as per Military Standard 105 E.
  • After sampling put the ‘SAMPLED’ stamp in sampled packs (containers/boxes/rolls) in ‘Black ink’ on the `Quarantine’ label affixed on each pack in such a way that more than half stamping on quarantine label and remaining on packs (boxes/rolls/containers).
  • Stamping shall be done only for those packs that are sampled with the sign. and date of sampling and keep the material at designated place (At the respective location code, if specified in GIM).
  • Do not mark the `SAMPLED’ stamp where the sample is supposed to return to the packing material store.
  • During visual inspection of the consignment, the material should be free from visual defects like…
    • Improper printing,
    • Improper pasting,
    • Alignment of printing,
    • Loose winding or telescopic,
    • Wet & damaged,
    • Objectionable odor,
    • Cut, dent, damage core or edge,
    • Wrinkles in case of foils,
    • PVC or PVC coated PVDC film,
    • Sticking of show boxes, oil, grease, dirt, dust, fiber particles, stone, insects, etc.
  • Remove the minimum 3 meters of
    • Printed Aluminium foil,
    • Plain Aluminium foil,
    • PVC film and
    • PVC coated PVDC film for visual inspection
  • Then cut a minimum 3 meters of printed Aluminium foil and 2 meters of plain Aluminium foil, PVC film and PVC coated PVDC film for complete analysis in the laboratory as per sampling plan.
  • For show box, package insert, corrugated box, printed pressure sensitive labels, HDPE bottles, BOPP tapes, poly bags, applicator, etc. sample withdrawn for visual inspection and complete analysis as per sampling plan.
  • Packing material ‘Visual inspection checklist and sampling report of packing material’ (ref. Attachment – 2) shall be filled during sampling.
  • Spot analysis of packing material during sampling.
  • Physical Appearance of the consignment (Improper packing, dust, dent, damage core, wet condition, etc.)
  • Visual Inspection of the sample (Printing clarity/alignment, loose winding/telescopic, wrinkles, improper pasting/sticking, objectionable odor, rough edges, oil, grease and dirt, fiber particles, etc.)
  • Sampling Scheme of Packing Material as per AQL:
  • Number of packs to be sampled from the total number of packs received as per table – 1.
  • Number of samples to be taken for visual inspection and for complete analysis as per table – 1A.
  • For visual inspection of AQL, consider sample size from the consignment as given in table -1B and record observations in the ‘visual inspection checklist and Sampling report of packing Material’. Ref. attachment-2.
  • The visual inspection of samples shall be carried out in stores for Acceptance Quality Level (AQL) for acceptance criteria of defect attributes like Critical defects 0 %, Major defects 1.0 %, and Minor defects 2.5 % as per details given in Table- 1C.

                 Table – 1: Number of packs to be sampled from the total number of packs received.

Total no. of packs receivedTotal no. of packs to be sampled
2 to 82
9 to 153
16 to 255
26 to 508
51 to 9013
91 to 15020
151 to 28032
281 to 50050
501 to above80

Table – 1A: Number of samples to be taken for complete analysis & for visual inspection.

Batch or Lot Size (Number)Samples for visual inspectionSamples for complete analysis
2 – 822
9 – 1533
16 – 2553
26 – 5084
51 – 90135
91 – 150205
151 – 280327
281 – 500508
501 – 12008010
1201 – 320012512
3201 – 1000020015
10001 – 3500031519
35001 – 15000050023
150001 – 50000080029
500001 and over125036

Table – 1B: Sampling plan for Visual Inspection

      Lot sizeSample sizeAcceptance criteria  (Normal inspection)
Critical 0 %Major 1.0 %Minor 2.5 %
ARARAR
2 to 82010101
9 to 153010101
16 to255010101
26 to 508010101
51 to 9013010112
91 to 15020010112
151 to 28032011223
281 to 50050011234
501 to 1,20080012356
1,201 to 3,200125013478
3,201 to 10,00020001561011
10,001 to 35,00031501781415
35,001 to 150,0005000110112122
150,001 to 500,0008000114152122
500,001 and over12500121222122

A= Acceptance No.    R= Rejection No.

Table-1C: Acceptance Quality Level (AQL) Defects Criteria for Visual Inspection

Procedure: Visually inspect number of samples as per the table 1B : Military standard 105    E.
Critical defects 0%: A critical defect is one that will render the finished product unsafe. Because this represent a potential risk to the patient. For acceptance and rejection refer Table 1B. Major defects 1.0% : A major defect is a defect, other than a critical defect, that is likely to cause non-conformance of product during manufacturing,testing, shipment, storage or use. Such failures do not constitute a potential risk to the patient. For acceptance and rejection refer Table 1B. Minor defects 2.5% : A minor defect is a non-conformance that may detract product elegance, but is expected to have little or no effect on the suitability of the Finished Product for its intended use. For acceptance and rejection refer Table 1B.

(Sampling of Packing Material)

Material NameCritical defectsMajor defectsMinor defects
Printed Show boxMixing of show box other than mentioned productLocking defectsImproper Creasing
Text matter missing / colour missingImproper pastingFolding (Improper)
Embossing missing  Sticking of cartonsColour shade variation
Smudgy Printing/ Shifting of text matters
Wet and dirty cartons

(Sampling of Packing Material)

Plain show boxMixing of show box other than mentioned productlocking defects Improper pastingImproper Creasing
Folding (Improper)
Colour shade variation
Sticking of cartons
Wet and dirty cartons

(Sampling of Packing Material)

Printed LabelsMixing of labels other than the mentioned product.Improper pastingColour shade Variation
Text matter missing / colour missingSmudgy Printing / Shifting of text matters
Wrong winding directionImproper cutting
Wet and dirty labels

(Sampling of Packing Material)

Printed Package Inserts (Leaflets)Mixing of leaflets other than the mentioned product.Improper cuttingColour shade Variation
Text matter missing / colour missingSmudgy Printing
Hole or cutTorn leaflets
Shifting of text matters

(Sampling of Packing Material)

Poly bagsMixing of Poly bag other than mentioned productHole / cut defectsBase information
Extraneous dust or particulate matterBottom sealing
Wet and dirty

(Sampling of Packing Material)

BOPP Tape (Printed / Plain)  Extraneous dust or particulate matterTornColour shade Variation
Missing of company Logo (If applicable)Core damaged
Stains

(Sampling of Packing Material)

Corrugated Boxes (Shipper)  Mixing of shipper other than mentioned productTorn and damaged boxCracks developed on the edges.
Layer separation
Rusted staplesWet and dirtyColour shade Variation
Silica gelPresence of Extraneous matterFinishing of canisterBase formation

(Sampling of Packing Material)

Material NameCritical defectsMajor defectsMinor defects
HDPE bottles /caps / spoon/ tablet applicatorMixing with other than mentioned productDamagedColour shade variation
Extraneous matter
Presence of Black particlesRough Edges
Presence of dents
Cracked containers, Hole or cutWet and dirty

(Sampling of Packing Material)

Plain Alu. Foil(Stip & Form Pack) / PVC Film/PVC- PVDC FilmMixing of foil/films roll other than mentioned productLoose winding and Telescopic windingColour shade variation
Poorly damaged coreWrinkles & brittle
Wrong winding directionDifferent colour stains on the foil
Wet and dirty

(Sampling of Packing Material)

Printed Aluminium FoilMixing of foils roll other than mentioned productLoose winding and Telescopic windingColour shade variation
Text matter & colour missing or cuttingSmudgy printing / shifting of text matters
Poorly damaged coreDifferent colour stains on the foilNumber of joints (NMT 2)
Wrong winding direction
Wet and dirty

                 * Functionality test as per the respective specifications

  • Randomly select the boxes and withdraw approximately equal quantities of sample from the selective boxes.
  • Check the samples as per AQL. After the checking of Acceptance Quality Level of Packing material put the samples (except the material which are defective) in same boxes in such a way that the sample quantity of boxes shall remain same as per initial quantity.
  • Left over sample shall be kept in last sampled box.
  • E.g ; Suppose 25 packs of show box are received and received quantity is 10000 as per GIM, then according to Military Standard 105 E, total no. of box to be sampled is 5 and total sample quantity is 200.
  • So collect 40 nos. show box from each selected box. Check the each ups of multiple’s sheet and perform the spot analysis. After spot analysis, segregate the 15 nos. show box for QC analysis.
  • Return the same withdrawn show box quantity (40 nos.) to respective sampled box (1 to 4 no. box) and remaining left over show box (25nos.) shall be kept in last sampled box (5 no.).
  • For complete testing of packing material as per respective specification, draw the quantity of the samples required for analysis. Perform the complete analysis on number of samples as per table 1A. BOPP tape, poly bag etc. where complete testing shall be done on 3 numbers.
  • In case of silica gel & BOPP tape, samples are return back to PMS after analysis.
  • In case of corrugated box, visual inspection shall be done as per AQL and dimension shall be checked for 3 numbers of corrugated box at the time of AQL sampling.
  • Dimension shall be mentioned in attachment-2 (Visual inspection check list and sampling report of packing material).
  • Close inner and outer packing properly after sampling with imprinted QC SAMPLED BOPP tape affix “sample” label on sampled materials. Ref. annexure-2.
  • Deduction of sample quantity in ERP/SAP System (Sampling of Packing Material):
  • In case of plain/printed foil, PVC, PVC coated PVDC film, poly bag etc., the    sample quantity remove in meters and numbers form but sample quantity shall be deducted in ERP/SAP system in Kilogram form as per below.
Sr. No.Material NameThicknessSample quantity in meters/nos.Sample quantity in Kgs. Approx.
1Printed Alu. blister foil0.025 mm3 meters/Roll0.05 Kg.
2Printed Alu. strip foil  0.04 mm3 meters/Roll0.12 Kg.
0.03 mm3 meters/Roll0.1 Kg.
3Printed paper based laminate foil0.02 mm3 meters/Roll0.12 Kg.
4Plain Alu. Blister foil0.025 mm2 meters/Roll0.03 Kg.
5Plain Alu. strip foil0.04 mm2 meters/Roll0.1 Kg.
0.03 mm2 meters/Roll0.08 Kg.
6Alu-Alu form pack foil0.045mm2 meters/Roll0.12 Kg.
7PVC Film0.25 /0.3/ 0.35 mm2 meters/Roll0.15 Kg.
8PVC coated PVDC film0.25 /0.3/ 0.35 mm2 meters/Roll0.2 Kg.
9Poly Bag (All size)150/200 gauge3 nos.0.15 kg.
  • Acceptance Criteria:
  • All results should comply as per the respective specification.
  • In case of the sample does not complies the AQL then material shall be rejected.

8.0   ANNEXURES OF SOP – SAMPLING OF PACKING MATERIAL:

Annexure-1: Packing Material Inward Register.

Prepare the logbook with the following table contents…

  • SR. No.
  • GIM Date
  • GIM receipt Date
  • Item Name
  • Item Code
  • GIM No.
  • A.R. No.
  • Receipt Qty.
  • Mfg. by/ Supplied by
  • Sampled by / Date
  • Analysed by / Date
  • Released Status
    • Approved by / Date
    • Rejected by / Date
  • Remarks

Annexure-2: Visual Inspections Checklist and Sampling Report of Packing Material.

  • Item Name                  :
  • Item Code                               :
  • GIM No.                     :
  • A.R. No.                     :
  • Mfg. / Supplier Name :
  • Date of material receipt          :
  • Quantity Received                  :
  • Number of packs received      :
  • Number of packs sampled      :
  • Visual inspection quantity      :
  • Quantity for complete analysis           :
  • Spot Analysis of the sample (Put mark)
  • Physical Appearance            :Complies / Does Not Complies
  • (Improper packing, dust, dent, damage core, wet condition, etc.)
  • Visual Inspection (As per AQL)      : Complies / Does Not Complies / NA
  • (Printing clarity/alignment, wrinkles, loose winding, telescopic, improper, pasting, sticking, objectionable odor, rough edges, oil, grease and dirt, fiber particles, etc.)
  • Storage condition                    : Complies / Does not comply
  • Others (if any)             :

Annexure-3: Sampled Stamp.

  • Sampling of Packing Material

Annexure-4: Sample Label.

Quality Control Department SAMPLING OF PACKING MATERIAL
Item Name …………………………………………………………..
Batch No. ……………………… A.R. No. ……………………..
Sampled quantity ………………………………………………..
Roll / Pack No. …………………………………………………….
Mfg. / Supplied by ……………………………………………….
Signature …………………….. Date……………………………..

Leak Test Apparatus – Operation and Cleaning SOP

Standard Operating System (SOP) for Operating, cleaning of Leak Test Apparatus which is used to check the leak seal test of packed strips, blisters, sachets, and bottle packs.

Procedure For Leak Test (Leak Test Apparatus)

PURPOSE:

  • The purpose of this Standard Operating Procedure (SOP) is to describe the detailed procedure for checking the Leak seal test of packed Strips, Blisters, Sachet packs, and Bottle packs.

SCOPE:

  • This procedure is applicable to carry out the leak seal test at the pharmaceutical plant of the below-mentioned packs.
    • Blisters (ALU-PVC, ALU-PVC/PVDC & ALU-ALU).
    • Sachet Pack
    • Bottles Pack

 PROCEDURE – SOP FOR LEAK TEST APPARATUS:

  • Equipment: Leak Seal Test Apparatus shall be used to perform the leak seal test.
  • Checks and precautions during handling of Leak Test Apparatus:
  • Wear hand gloves while the opening of strips/blisters/sachets/bottles.
  • Use potable water for testing purposes.
  • The perforated disc should be immersed in Water of leak seal test apparatus
  • Before the starting of any batch, the leak test shall be carried out by the production and the same shall be verified by Quality Assurance (QA).
  • The frequency for leak seal test – Leak Test Apparatus:
  • Leak seal test shall be performed at the start of operation and at an hourly interval during the stripping operation.
  • In the case of Blister, Bottle filling and Sachet Leak test shall be performed at an interval of 2 Hours.
  • After every change over of lidding foil.
  • Completion of any maintenance work.
  • After the restart of a machine if more than 30 minutes stoppage in the packing department
  • In case of small batch (batch completed within 2 hours), leak test to be performed at the start, middle, and at the end of the batch.
  • Sampling for Leak Test :
  • The total number of strips/ blisters sealed by the full rotation of the sealing roller or plate shall be subjected for leak seal test.
  • In the case of bottles, two consecutive bottles shall be subjected for leak seal test (after sealing induction stage).
  • In the case of Sachet, five sachets are used for performing a leak test.
  • Part I – General Instruction – SOP for Leak Test Apparatus:
  • The operator of the respective area shall calculate the required number of strips/blisters/sachet/bottles for leak seal test as per defined frequency.
  • The number of samples required for the leak seal test shall be estimated by considering the type of change parts used for packing.
  • Respective operator/Production shall fill the leak seal test intimation slip as per Annexure-I.
  • All the samples collected for leak seal test shall be collected in a self-sealing poly bag and labeled the same as per Annexure-II.
  • Leak seal test sample along with intimation slip shall be forwarded by the operator/line officer to centralize the leak seal test area.
  • Representative of centralize leak seal test area shall ensure the receipt of sample & shall take the signature of concern on the leak seal test intimation slip, along with date and time.
  • After receipt of the sample from respective areas the representative of the leak seal test area shall log the details in the leak seal test logbook, (first in, first record, and test) concept shall be adapted.
  • The detail shall be recorded as per annexure-III.
  • Part II – General Instruction – SOP for Leak Test Apparatus:
  • Perform the testing of the leak seal test as per instruction/condition specified in the sample intimation slip.
  • After completion of testing defoiling of strips/blister to be done and check any leakage in the same.
  • Destroy the Strips/blisters/sachets/bottles and its contents after leak seal test.
  • If any discrepancies observed after testing, then inform the respective production/quality assurance for further course of action.
  • Production/quality assurance shall investigate for leak seal test failure and take necessary action.
  • Record the details in the respective batch packing record.
  • If required stop the machine.
  • Resume the line only after the implementation of necessary actions and removal of discrepancies.
  • Reconciliation of tablets used for leak seal test shall be ensured by Packing/Quality Assurance at the time of batch completion and shall perform the necessary entry in BPR.
  • Cleaning of leak seal test apparatus shall be done on a daily basis and date, Equipment ID, checked and remark column shall be recorded in Annexure –III. Put NA in not the relevant column.
  • In the case of Leak Test Failure:
  • Intimate the Department Head and QA
  • Quarantine the packed shipper between in-process checks Interval.
  • Perform random recheck of packed shipper for open pocket, sealing defective Strip /blister, etc.
  • Perform random sampling and do the leak test, if it passes inform QA and continue Packing activity.
  • In case of leak test fail, raise the observation, and carry out the investigation to find out the root cause and draw the corrective action.
  • In the case of Power Failure restart the apparatus and perform the leak test.
  • Procedure for Leak seal Test Apparatus (Model – NE/102):
  • Immerse the strips/blisters/sachet/bottle in a vacuum apparatus half-filled with water.
  • Check that the strips/blisters/sachet/bottles are completely submerged in water after covering with the disk and lid.
  • Apply vacuum till 350 mm ± 10 of Hg. (14 inches) equilibrium achieved.
  • Close the stopcock in such a way that the equilibrium maintained for 3 minutes.
  • Hygroscopic products (e.g Encorate/Decorate/Macorate/Korandilgroup etc.) apply vacuum till 381mm of Hg10mm of Hg (15 inches) achieved and follow the procedure as given above.
  • After 3 minutes open the stopcock and release the vacuum and wait for 1 minute.
  • Open the lid, remove strips/blister/ sachets/bottle and wipe off the water from the surface of the strips, blisters, sachets, and bottle with a clean dry duster.
  • Open the strips/blister/sachets/bottle by scissors/manually and carefully remove the content from the strips/blister/sachets/bottle by manually on a dry plate.
  • Examine the contents for stickiness or wetness.
  • If any product becomes sticky or wet then the blister /strip considering as failure in leak test
  • If any wet content observed, then inform to packing/Q.A.
  • Collect the used content of the leak seal test in a polybag for non-recovery and destroy.
  • Record and reconcile the same in the BPR.
  • Procedure for Leak seal test Apparatus (Model-LT-101P) :
  • Place the test sample in the vacuum apparatus filled with water to the desired level.
  • Connect the vacuum tube between desiccator and the “VACUUM INLET” nozzle, provided on the back panel of the instrument. Switch “ON” the power switch.
  • Press “Set” Key and set “vacuum” at 350 mm Hg ± 10 mm (14 inches).For Hygroscopic products (e.g Encorate/ Decorate/Macorate/Korandil group etc.) set “vacuum” at 381 mm Hg ± 10 mm (15 inches) by using UP and Down key.
  • Press “Set” Key and set “HOLD TIME” by using the UP and Down key.
  • Set HOLD time for 3 minutes.
  • Press “Set” Key and set “USER ID” by using up and down key.
  • Press “Set” Key and enter “NO OF SAMPLE” as per requirement by using the UP and Down key.
  • Then press “Set” Key and enter “B.No. XXXX” by using UP and Down key.
  • After all the data entry, press the enter key after that press “Run” key and wait for 03:00 min (While pressing a run key it shows a red indicator blowing in the m/c.).
  • Release the vacuum slowly after the hold time over the vacuum.
  • Open the lid, remove strips/blister/ sachets/bottle and wipe off the water from the surface of the strips, blisters, sachets, and bottle with a clean dry duster.
  • Open the strips/blister/sachets/bottle by scissors/manually and carefully remove the content from the strips/blister/sachets/bottle by manually on a dry plate.
  • Examine the contents for stickiness or wetness.
  • If any wet content observed, then inform to packing as well as Q.A., check for the cause and reset the machine and retest for the leak seal test.
  • Record the readings in the logbook.
  • Collect the used content of the leak seal test in a polybag for non-recovery and destroy it. Record and reconcile the same in the BPR.
  • Tolerance:
  • None of the content of the strips/blister/sachets/bottles found moist /wet after the leak seal test.
  • Cleaning procedure for leak test apparatus:
  • Clean the instrument daily as follows:
    • Clean the vacuum apparatus with potable water and scrub with the help of scrubber.
    • Rinse the vacuum apparatus with potable water for not less than 1 minute.
    • Finally, rinse the vacuum apparatus with potable water for not less than 1 minute.

7.0   ANNEXURES:

Annexure 1: Leak Seal Test Intimation Slip

Product NameGeneric Name
Batch No.Line No.
Sample Qty. in UnitSpecification350 mmHg ±10 of Hg. (14 Inches)
381 mmHg ±10 of Hg. (15 Inches)
DateTimeShipper No.Sampled byReceived ByLeak Seal Test Equipment ID.Leak Test Done ByResult (Pass/Fail)Checked ByNon recovery Destruction Yes/No
Total Qty. of Nonrecovery………………… Units.

Annexure 2: Leak Seal Test Sample Label

Leak seal test Sample label
Product Name:
Batch No.:
Line No.:
Sampled  By:(Signature)

Annexure 3: Leak Seal Test Apparatus Log Book

Dept.:Area: Equipment Name:
DateTime of samplingProductBatch No.Line NoTime of testingLeak seal test Equipment ID.Checked By NameObservation PASS/FAILRemarks (if any)

SOP For Dispensing of Packaging Material

Standard Operating Procedure for Issuance / Dispensing of Packaging Material (Packing Materials) like Corrugated box, Primary Packaging Material (PPM), Secondary Packing Material, Aluminum Foils, BOPP tape, PVC Foils, etc. which is required to pack the drug product.

Procedure for Packing Material Dispensing / Issuance

PURPOSE:

  • The purpose of this SOP is to define the procedure for the issuance of packing materials.

SCOPE:

  • This procedure is applicable to all packing materials to be issued to production for the packaging of drug product in the pharmaceutical manufacturing plants.

REFERENCES – SOP FOR ISSUANCE OF PACKING MATERIAL:

  • In house.

PROCEDURE FOR ISSUANCE OF PACKING MATERIAL:

  • Get the packing Metis/ERP/Other Software/Manually generated work order issue (Material pick up list) from the production department duly signed by production person.
  • Material is dispensed as per Metis/ERP/Other Software/Manually generated work order issue (Material pick up list) as per (Annexure 1).
  • Collect the packaging material as per the location code mentioned on the work order issue (Material pick up list) on pallets/cage trolley.
  • Check net weight on quarantine label in case of aluminium foil, PVC and PVDC film and in case of show boxes, inserts, sample boxes, thermo col boxes, HDPE bottles, caps and sticker labels check the quantity mention on quarantine label.
  • Ensure that before issuing of primary and secondary packaging material, first scan the barcode printed on the quarantine coupons.
  • Arrange issued primary and secondary packing material for a batch in the cage trolley. Use separate cage trolley for different batches. Print the “Dispensed Material” Metis/ERP/Other Software/Manually generated label as per (Annexure 4) affix on cage trolley.
  • Counter check all the materials against the work order issue (Pick up List).
  • Counter check all the materials against the outer label by opening each intact pack.
  • Dispense the loose quantity of packing materials in transparent polybag. Ensure the quantity by verification i.e. weighing or by counting.
  • Affix or put a status label (Annexure 2) on the polybag for easy traceability.
  • Final check-up of the loose quantity, as well as the intended quantity, shall be verified by packaging material store representative during dispensing.
  • Segregation of dispensing printed packaging materials or the dispensed packaging material shall be ensured at all steps of issuance.
  • Remaining quantity transfer on the same location with the status label affixed on the box as per (Annexure 3) and written “LOOSE” with permanent marker on the box.
  • Call production person to cross-check the issued material and take the signature on unconfirmed material pick up the list after his verification.
  • Handover Metis/ERP/Other Software/Manually generated confirmed work order copy (Annexure 5) to packing officer and take signature on store copy and transfer material to packing department after locking it with a one-time usable cable tie.
  • Note: Use the following guideline to packing materials-
Sr. No.ItemsCounting procedure
1Shippers, Silica gel, Coolant bags & BOPP tape.By physical counting
2Show boxes, Inserts, Physician sample boxes, Thermocol Boxes, HDPE bottles, and caps/Aluminium poly laminated bags.Intact packet wise by arriving quantity mentioned by the supplier/manufacturer on the packet. Loose qty. by physical counting.
3Aluminum foil, PVC & PVDC films.As per the roll no. mentioned on the packing material issue order and quarantine label affixed on the roll.
4Sticker LabelsAs per the roll no. mentioned on the packing material issue order and quarantine label affixed on the roll.

ANNEXURES:

  • Material Pick-up List (Annexure 1).
Material Issue Order              
W O Issue No. :          Department   :             W O Issue Date :       
W O No.         :                                   W O Date      :
Dispensed Date    :
                                                                         
Product             :
Product Code    :         BOM Code :   Batch No. :
Batch Size         :         Unit            :      Operation :    Process                  : 
  • Loose Material Dispensed Label (Annexure 2).
ITEM CODE  : ____________________      ITEM NAME : ____________________ A.R. NO.        : ____________________ LOOSE QTY. : ____________________ CHECKED BYSTORE SIGN/DATE: ____________________
  • Remaining Quantity Label (Annexure 3).
ITEM CODE  : ____________________      ITEM NAME : ____________________ A.R. NO.        : ____________________ REMAINING QUANTITY: ____________________ CHECKED BYSTORE SIGN/DATE : __________________
  • Dispensed Material (Annexure 4).

 DISPENSED MATERIAL    

———————————————————————————————————               

Product :

Batch No.              :                              Lot :

Stage      :             

Container No.       :             

Material Dispensed By       :

Material Dispensed Date:              Work Order Issue No.         :

———————————————————————————————–

  • Issue Material Order (Annexure 5).

Issue Order                

W O Issue No. :          Department:             W O Issue Date :       

W O No.         :                                   W O Date      :

 Dispensed Date    :

Product             :

Product Code    :         BOM Code :   Batch No. :

Batch Size         :         Unit            :      Operation :    Process                  : 

SOP on Operation of Colloid Mill

The purpose of this standard Operating Procedure (SOP) is to lay down a procedure for operation of colloid mill.

This procedure is applicable to operation of colloid mill at manufacturing facility of Pharmaceutical Industry.

  • PROCEDURE:
    • Ensure that area is cleaned as per SOP.
    • Ensure that all the parts of colloid mill are cleaned as per SOP.
    • Ensure mains are ‘OFF’ and plug top is removed from socket.
    • Diagram:
  • Check that screws on rotor (3 in No.) are properly fitted.
    • Rotate the rotor by hand and ensure free movement.
    • Place the outer ring and turn it clockwise to match scale with indicator mark (scale to be set as per product requirement).
    • Tighten the handles on the sides so that ring is locked in position.
    • Place the neoprene food grade gaskets followed by top ring and hopper.
    • Tighten the bolts of hopper.
    • Put ‘ON’ the mains and check direction of rotation (direction of rotation should be long the arrow marked on the body of the machine).
    • Fix the recirculation/outlets nozzle along with gasket.
    • Take the line clearance as per SOP and record the line clearance activity in Annexure.
    • Take a trial with purified water.
    • Ensure absence of leakage or abnormal noise. Affix ‘USE FOR’ label on machine with product name, date and sign of production officer.
    • Feed the solution/suspension to be milled in hopper and switch ‘ON’ the Colloid mill.
    • Mill the solution/suspension in single pass or multiple pass (recirculation) by adjusting the knob   on the outlet nozzle (as per product requirement). Check the grittiness of out coming suspension.
    • Rinse the colloid mill with solvent/purified water.
    • Switch ‘OFF’ the colloid mill.
    • Affix ‘TO BE CLEANED’ label on the hopper with Equipment no., previous product, Batch No., Date, and Signature of production officer.
    • Record cleaning activity as per SOP in Cleaning and Usage Log of Equipment and Area.
    • Calibration :
      • RPM of colloid mill every 12 months by outside party.
      • Frequency every 12 months.

NOTE:      1.    Colloid Mill Should Be Cleaned Immediately After Use.

                   2.    Set The Colloid Mill At ‘0’.

                   3.   If Colloid Mill produces any abnormal noise should be reported to

                         Engineering department immediately.

                   4.   Never live machine with material overnight.

                  5.   Check the direction of rotation of the rotor before starting of the

                         machine. ‘Direction of rotation of the mill must be clockwise’.

  • TRAINING:

As per Employee training SOP

  • DISTRIBUTION:

As per SOP for SOP

  • ANNEXURE:

Nil.

SOP for Handling Punches and Dies

The purpose of this standard Operating Procedure (SOP) is to lay down a procedure for handling and control of punches and dies, used during compression.

This procedure is applicable for procurement, usage, cleaning, maintenance and disposal of all the punch sets (i.e. new and in use) and related testing kits, i.e. punch height checking kit and punch polishing kit used in Tablet department at manufacturing facility of Pharmaceutical Industry.

  • PROCEDURE:
    • ORDERING NEW PUNCHES AND DIES:
      • ORDERING OF NEW SET OF PUNCHES AND DIES OR ORDERING OF EXISTING PUNCH SET WITH NEW PARTY.
        • Drawing’ for Upper punch, Lower punch and Die should be prepared by the manufacturer as per the specifications given or as per sample punch set. 
        • After primary approval of the drawing, sample punch set (1Upper punch, 1 lower punch and 1 die) will be received from the supplier.
        • Department Head will approve ‘Sample punch set’ after taking a trial on the machine.
        • Standard specification of punch set for respective product is prepared after successful trial and approval of sample  write down in appropriate Annexure.
        • After approval of the ‘Sample punch set’, Purchase order for the full set of punches and dies will be initiated by the Purchase Department Head, and authorized by the Unit Head, giving following details:-
          • The total number of punches and dies required for Compression machine will be as follows.
          • Example :-  For 26 station m/c: 31 sets, For 32 station m/c: 37 sets, For 55 station m/c: 60 sets
          • Type of Tooling required e.g. D/B type.
          • Material of construction to be used (High Carbon High Chromium (HCHC) /Oil Hardened Not Shrinkable (OHNS)).
          • Engraving/laser etching of following details on individual punch
            • Serial number.
            • Name of the manufacturer (Short form) e.g. GMI for General Mechanical   Industries.
            • Date of Manufacturing (Month and Year).
            • Punch size in millimeter.
            • Any other Specifications/Special requirements like embossing, central break line,      beveled edge, chrome plating, groove on upper punches for rubber cups etc.
        • After receiving the consignment, punches and dies will be checked as per standard specification / sample punch set of respective punch set. Along with the following additional checks:-

Appearance (finishing of Punch set)

Damages (cracks/chips)

Height of punches (Working length)

Proper fitting of punches and dies on the machine

  • Record the observations in the  appropriate Annexure
    • Supplier should provide following documents with punch set :-

Drawing

Certificate of material of construction

Inspection report

  • ORDERING OF EXISTING PUNCH SET FROM SAME SUPPLIER:
    • Place the order to the manufacturer who had supplied earlier punch set   for the particular product.
    • Give one set to the manufacturer as a sample and repeat the step no. as above mentioned.
    • CHECKING OF PUNCHES AND DIES:
      • Each punch and die should be checked individually using the standard specification.
      • Check the details engraved on individual punch and die as above mentioned.  
      • For new punch set if supplier has provided all test documents then it should be taken for use after verification and QA approval based on in-house verification.
      • Checks for Punches:
        • Tip Dimension. Check individually UP and LP by vernier calliper.
        • Tip surface Check visually for scratches, damages, surface finish, cracks, pits, and spots and chrome plating (if applicable).
        • Body surface Check visually for scratches, damages, surface finish, cracks, pits, spot and chrome plating (if applicable)
        • Chamfer Check visually for angle, uniformity
        • Tips edge: Check visually for damages, cracks, sharpness and burr
        • Embossing

Check visually for letters, flattening of letters, burr, roughness, cracks and deep score.

  • Central Break Line

Check visually for position, flattening, roughness, cracks, deep score

  • Checks for Punches:Inner dimensions- Inner dimension of bore with help of vernier calliper and by inserting lower punch in it.   Inner surface, Check visually for scratches, damages, surface finish, cracks, pits, spots    and chrome plating (if applicable).Body surface, Check visually for surface finish, level uniformity, edges (both upper and lower surfaces)

NOTE: Check individual die by inserting upper and lower punch in it and check for its freeness

  • Frequency Of Checking The Punch SetWhen the punch set is new, Quality Assurance should certify the punch set. (Annexure V).   Visual checking of Punch set should be done after every batch and at the time of fixing or removing the punch set from machine.
    • PUNCH HEIGHT CHECKING:
      • Take the punch set from the punch set cabinet.
      • Clean all the upper and lower punches as per SOP and arrange them in sequence with the help of their serial numbers.
      • Assemble the punch height variation checking equipment.
      • Clean the platform of punch height checking equipment.
      • Place the Calibrated Standard Hobb (supplied along with equipment) on platform and adjust it below the dial knob.
      • Set dial indicator to ‘zero’ by rotating the dial of equipment. Recheck the ‘zero’ setting of dial indicator with standard Hob and check the height of punches as per following instructions.
      • Check the ‘Variation Working Length’ for deciding the suitability of the punch In all types of punches viz. Concave, Flat Beveled Edge etc.
      • Keep the punch in ‘Head DOWN and Tip UP’ position while checking the punch height i.e. Critical Working Length and find out the constant minimum reading on the dial by moving the tip-surface of punch against the pointer (actuator) of the dial gauge.
        • Check and record the variation in height of all punches in Annexure I Discard the punch if the difference is more than + 0.003 inch  (in case of round shaped) and +0.005 inch (in case of other than round shaped  than the standard height 133.600 mm).
        • Clean the platform and dismantle the equipment. Keep the equipment parts, dial and standard punch in the respective drawer.
        • Frequency of punch height checking is as per following table.
Punch set typePunch set lifeHeight-checking frequency
Circular4 million tabs/set2 million tabs/set
Other than circular2 million tabs/set1 million tabs/set
Double layered (circular)2 million tabs/set1 million tabs/set
Double layered (noncircular)1 million tabs/set0.5 million tabs/set

       1 set = 1 upper punch + 1 lower punch + 1 die

NOTE:

  • Punch height shall be checked as per height checking frequency or one year, whichever is earlier.
    • Always consider the minimum reading on the dial indicator, which shows the deepest point on the punch tip surface.
    • In case of embossed punch tip with break line the reading should be taken by adjusting the pointer on plain surface at the same location on each punch.
    • POLISHING OF PUNCHES AND DIES:
      • PUNCH SHOULD BE POLISHED WHEN.
        • There is burr or claw on punch tip.
        • Punch tip turns black.
        • Roughness on the tip is observed.
        • Sticking/picking problem is observed.
        • Appearance of tablet becomes dull.
      • DIE SHOULD BE POLISHED WHEN.
        • There is ring formation inside the die-bore.
        • Die-bore surface becomes black.
        • Corrosion is observed inside die-bore.
        • Wear or drag is observed in die-bore
      • POLISHING OF PUNCHES AND DIES.
Tooling typePolishing toolPolishing material
PunchesNylon brushesEmery paste
DiesFelt bobEmery paste
  • FREQUENCY OF POLISHING THE PUNCHES AND DIES:As and when required (Whenever the above problems are observed)Use the equipment for polishing of punches and dies and recommended polishing compounds as per SOP.
    • ISSUE AND RECEIPT OF PUNCHSETS:
      • ISSUING A PUNCH SET.
        • Depending on the product and the compression machine, select a punch set for issuing it to the required machine.
        • Take the punch set from Punch storage cabinet and clean the punches and dies as per SOP .
        • After cleaning, check:
          • Total number of punches and dies in the punch set.
          • Suitability for their use by checking the tip surface, body surface embossing etc. of the individual punch and die.
          • Issue the exact quantity of punches and dies for setting on the machine and store the spare/remaining punches and dies back into the respective drawer. Make the entry in punch Stock Card in  appropriate Annexure NO

Note: For uniform wear and tear of the Punches and Dies, use the tooling in rotation of 5 sets during product to product changeover or every week whichever is earlier.

E.g. For first time from 1 to 26 and next time from 6 to 31 and so on…. (Use every punch set in rotation).

  • RECEIVING A PUNCH SET FROM THE MACHINE.
    • After completion of the compression of a batch or the production plan, dismantle the punches and dies from the machine.
    • Clean the punches and dies as per SOP and check all the punches and dies individually and store them into the respective drawer of cabinet or the box by applying a thin smear of non-toxic food grade oil (as per Standards).
    • Record the number of punches and dies received in Punch Stock Card in appropriate Annexure
    • CLEANING OF PUNCHES AND DIES AND DUST CAPS:
      • CLEANING OF PUNCHES AND DIES :
        • Cleaning of the punch set shall be performed as per the SOP for cleaning of Punch & Dies
        • In case of campaign manufacturing, the punch and die set shall be cleaned after 5 batches or 3 days, whichever is earlier.
      • CLEANING OF DUST CAPS :
        • Carry the dust caps in a virgin polybag to the washing area.
        • Keep all the dust caps fully immersed in water for half hour. Scrub the dust caps, if required.
        • Clean with approx 2 kg of filtered potable water & finally rinse with purified water.
        • Dry the dust caps using filtered compressed air.
    • DISPOSAL OF PUNCH SETS:
      • Punch set to be disposed when whichever of the following is earlier.
        • Punch set should be disposed when the set becomes incomplete due to reduction in the number of upper punches/ lower punches or dies because of rejection during the usage of punch set.
        • A full set (upper punch/lower punch/die) should be disposed when it becomes unusable due to damage to the tip/head/body of the punch or die during handling and usage of the punch set or due to corrosion.
      • Procedure of disposal:
        • Collect all the defective upper punches/lower punches and dies along with incomplete punch sets, which are to be disposed..
        • Record the details of all these defective punches and dies and in Annexure III and prepare a ‘Scrap Transfer Note of all these punches and dies.
        • Deface the punches and dies with the help of grinder and transfer the punches and dies to the scrap yard and dispose them.
        • Disposal activity should be done only after approval by the Head- production/ Head – QA and Unit Head and by taking all the necessary safety precautions.
NOTE:
  • Punch trolley should be used to carry the punches and dies from storage area to compression area and back.
    • Punches should be stored in plastic sleeves.
    • Dial gauge and Standard Hobb should be calibrated at every year.
  • TRAINING:
    • As per SOP For Employee Training
  • DISTRIBUTION:
    • As per SOP ON SOP
  • ANNEXURE:

Annexure I   : Punch Height Checking Record.

Annexure II : Punch Stock Card

Annexure III  : Punches / Dies (Punch set) DestructionRecord.

Annexure IV : Standard Specification

Annexure V: Punch and Dies Certification

SOP for Preparation of 2.5% w/v Caustic soda solution

The purpose of this standard Operating Procedure (SOP) is to lay down a procedure for preparation of 2.5% w/v caustic soda solution.

This procedure is applicable for preparation of caustic soda solution used for cleaning of equipment and accessories in pellet section at manufacturing facility of Pharmaceutical   Industry.

  • PROCEDURE:
    • PREPARATION OF 2.5 % W/V CAUSTIC SODA SOLUTION:
      • Take the necessary acessoceries such as SS container, acid – alkali proof gloves and safety goggles.
      • Take 10 lt. Purified water in a clean SS container.
      • Take 250.00 Gms of Sodium Hydroxide pellets and add it into purified water slowly. Then mix this gently using SS spatula and keep it aside for five minutes for cooling.
      • Label the prepared solution properly.
      • After the completion of the operation destroy the remaining cleaning solution by diluting sufficiently and pouring into drain in washing area.
      • Use freshly prepared caustic soda solution only.
  • TRAINING:
  • As per SOP On Employee Training
  • ANNEXURE:

Annexure I    : Record of 2.5 % w/v Caustic Soda Solution Preparation and     Destruction of Unused Solution.

SOP on Visual Checking Of Pallets

The purpose of this standard Operating Procedure (SOP) is to lay down a procedure for the guidelines for checking of the pellets before Bulk packing and Capsules filling.

This procedure is applicable for guidelines for checking of the pellets before Bulk packing and Capsules filling at manufacturing facility of Pharmaceutical Industry

  • PROCEDURE:

Before bulk packing or Capsules filling, visual checking of the pellets should be done for the following:

The shape of the pellets should be spherical and uniform.

The size of the pellets should be such that no unusual bigger pellets are observed, than that of the standard size as specified in the respective batch manufacturing record for the product.

The pellets should be free from agglomerates, broken pellets and fines.

The pellets should be free from Husks.

The pellets should be checked for any lumps / cake formation.

In case of any abnormal observation, resizing must be done through the sieves as specified in the BMR of respective product to remove agglomerates, broken pellets, fines or husks. The same should be recorded.

Check the shade of the pellets and ensure that there is no shade variation.

  • TRAINING:

As per SOP on employee Training                      

  • DISTRIBUTION:

As per SOP OF SOP  

  • ANNEXURE:

Nil

SOP on Procedure for the Operation of Fluidized Bed Dryer (FBD)

OBJECTIVE  :

The purpose of this SOP to describe the procedure for the operation of fluidized bed dryer (FBD).

SCOPE  :

This SOP is applicable for operation of fluidized bed dryer located in the tablet production department at Manufacturing site..

Equipment Name               :  Fluidized Bed Dryer.

Equipment ID No.               :

Manufactured by                 :

RESPONSIBILITY :

Production Officer/ Executive shall be responsible to supervise the operation of fluidized bed dryer.

IPQA Officer/ Executive shall be responsible for verifying the operation of fluidised bed dryer.

Head Production shall be responsible to check the procedure is followed as per SOP.

REFERENCES :

Nil

ABBREVIATIONS:

SOP        :   Standard operating procedure.

IPQA       :   In Process Quality Assurance.

FBD        :    Fluidized Bed Dryer.

I.D. No.  :     Identification Number 

DEFINITIONS :

Nil

GENERAL INSTRUCTIONS :

Check the cleanliness of fluidized bed dryer, its part and area.

Check the ‘CLEANED’ status label available on fluidized bed dryer.

Check the integrity of FBD bowl sieve and inspect the intactness of finger bag.

Check the proper fixing of finger bags, retarding chamber and bowl.

These FBD bags should be stored in separate bins and should be properly labeled.

Use dedicated FBD bag for each product and then check the proper fitting of FBD bag.

Check the steam filter before applying.

After charging powder in FBD bowl push the trolley in the dryer.

Check whether the earthling provided on the dryer are touching the FBD trolley.

Steam indicator valve to be checked during operation.

PROCEDURE :

Operation of Fluidized Bed Dryer:

Before starting the operation production officer / executive shall affix the activity status label having the details such as product name, B.No. Stage etc. to equipment and area and inform to IPQA officer / executive for line clearance.

Adjust the FBD bowl under the retarding chamber.

Switch ‘ON’ the mains.  Open the compressed air valve to apply pneumatic pressure 2.5 kg to 3.5 kg to lock the bowl.

While starting steam drying, Keep steam valve and by pass valve open initially to              drain the condensed water passing through the pipe. Close the condensed valve and adjust the steam valve so as to get the required air inlet temperature. Adjust the timer as per batch manufacturing record. 

Ensure that there is no leakage of air from FBD bowl and outlet.

Remove the container after shaking and rack the material. Again reset the product container and run for further drying. Take out the granules intermittently from the sampling points as and when required for checking the loss on drying.

After completion of operation shut ‘OFF’ the steam valve and air dry the material till the granules attains ambient temperature.

Shake the FBD bag and allow the material to settle down.

Release the compressed air pressure to unlock the FBD bowl from the retarding chamber. 

Remove the product container or go for the further process.

Affix “To be Cleaned “label to equipment .

Record the operation activity in equipment log sheet as per annexure – I.

Inspection of FBD bag shall be carried out for its integrity as per below given points

  1. Check bag for any small holes and torn.
  2. Check the finger of bag for stitches are intact.
  3. Check the corners of bag for intactness and stitches of corners .

Inspection of FBD bag shall be carried out for its integrity before and after the usage and record it in FBD bag usage record as per annexure –II.

After completion of operation clean the equipment as per cleaning procedure.

ANNEXURES:

Annexure – I   :  Equipment Log Sheet.

Annexure – II  :  FBD Bag Usage Record.