SOP on Cleaning of Glassware Used in Chemical and Instrument Analysis

The purpose of this SOP is to lay down a procedure for cleaning of Glassware Used in Chemical and Instrument Analysis.

This SOP is applicable for Cleaning of Glassware Used in Chemical and Instrument Analysis, in Quality Control Department at manufacturing facility of Pharmaceutical Industry.

PROCEDURE:

Collect the glass-wares viz., flasks, beakers, bottles, gooch crucible and silica ware etc., to be washed in a plastic tray.

First wash the used glassware with plenty of tap water.

Then scrub the glassware with 10% soap solution.

Rinse the glassware with plenty of tap water.

Again rinse 3 to 4 times with purified water.

Wipe the outer surface of the glassware with a clean cotton cloth.

Keep in Oven.

Always Use dried glassware for analysis.

Clean with Hot Nitric Acid  (Once in a fortnight):

Rinse the glassware with Hot Nitric Acid.

Allow it to stand overnight.

Rinse with plenty of tap water.

Finally rinse with purified water.

Wipe the outer surface of the glassware with a clean cotton cloth.

Use dried glassware.

Gooch crucible:

Fill the Gooch crucible with chromic acid mixture.

Allow it to stand overnight.

Rinse with tap water.

Apply vacuum and wash the crucible with tap water.

Then wash 3 to 4 time with purified Water.

Keep in oven.

Use dried glassware.

Silica and platinum crucible.

Rinse with chromic acid mixture.

Wash with tap water.

Wipe with a clean cotton cloth.

Ignite the crucible at 700º C temperature in a muffle furnace.

Cool and place in desiccators.

TRAINING:

As Per SOP on Employee Training

DISTRIBUTION:

As per SOP ON SOP

ANNEXURE:

Nil

REFERENCES(S):

Nil

SOP on Cleaning of Stainless Steel Scoop

The purpose of this SOP is to lay down a procedure to cleans the stainless steel scoop.

This SOP is applicable for Cleaning of Stainless steel scoop, in Quality Control Department at manufacturing facility of Pharmaceutical Industry

PROCEDURE:

Wash the scoops with distilled water.

Clean with water till it is visually cleaned.

Rinse with liquid (10%) soap solution and wash with water.

Finally wash with purified water.

Drain the water completely.

Dry the scoop at 60ºC temp. in an oven.

Wrap the scoop with polythene bag and keep in designated place.

TRAINING:

As per Employee Training SOP

DISTRIBUTION:

As per SOP ON SOP

ANNEXURE:

Nil

REFERENCES(S) Nil

SOP on Sampling Equipment

The purpose of this Standard Operating Procedure to lay down a procedure for cleaning of sampling equipment.

This SOP is applicable to describe the procedure of cleaning of Sampling Equipment in Quality Control Department at manufacturing facility of Pharmaceutical Industry.

PROCEDURE:

For Spoons :

Clean the sampling devices with Purified water to remove adhering material.

Finally rinse with purified water.

Check the cleanliness physically and clean again if it is necessary.

Dry it with compressed air.

Put the clean and dried equipment with proper wrap, with clean status label and keep it at appropriate place.

For sampling pipettes (Glass):

Clean the Glass sampling device with Purified water to remove adhering material and rinse.

Finally rinse with purified water.

Check the cleanliness physically and clean again if it is necessary.

Keep the washed tubes for draining on the stand meant for the same.

After the tubes are dried, wrap with clean status label and keep it at appropriate place.

For sampling Rods (Stainless Steel):

Clean the sampling rods with Purified water to remove obvious adhering particles.

Finally rinse with purified water.

Check the cleanliness physically and clean again if required.

Wrap with clean status label and dried equipment in a polybag & keep it in appropriates place.

After cleaning maintain the Cleaning Record of Sampling Equipment as per Annexure-I.

After cleaning the sampling tools can be used within 72 hours.

TRAINING:

As per Employee Training SOP

DISTRIBUTION:

As per SOP  ON SOP

ANNEXURE:

Annexure-I                  :  Cleaning Record of Sampling Equipment

SOP on Sampling of Raw Materials.

The objective of this SOP is to lay down a procedure for Procedure for Sampling of Raw Materials.

This SOP is applicable for Procedure for Sampling of Raw Materials in Quality Control Department at manufacturing facility of  Pharmaceutical Industry.

  • PROCEDURE:

Precautions:

Excipients should be sampled first & then followed by the active raw materials in case of sampling of both is planned.

In case starting materials are incoming from single product manufacturing site, the same shall be verified with approved vendor list then allow for reduce sampling for starting materials. (Refer annexure – II, Sampling check list).

If there are multiple samplings in a day of active RM, the sampling chemist should come out in to change room and discard the apron, gloves, mask, and cap. Wear fresh set of clothes, disinfect the hands & then enter the sampling room.

After sampling of their appropriate materials, sampling tools shall be cleaned as per SOP for cleaning of sampling tools.

In case of power failure during sampling activity close the material container as early as possible. Restart the sampling activity after 10 min of starting of booth and record the observations in sampling check list and usage record of Sampling room (As per Annexure II & Annexure IV).

If there are multiple samplings in a day then cleaning shall be performed after each sampling and record in the cleaning checklist and cleaning record of sampling room (As per Annexure V and Annexure IV).

Sampling Methodology:

On receipt of the GRN (Good Receive Note) / Testing Requisition Slip (TRS) from the store, Check whether the material is an active ingredient or an excipients as per approved vendor list.

All starting materials GRN shall be accompanied by the COA of the Manufacturer

All materials from biological origin should have a declaration for TSE & BSE for the list of materials from biological origin refer to Annexure -VIII

In case of material having CEP certification, check the update status of CEP declaration/CEP no.

In case of multiple batch number specified in the GRN, treat individual batch as one consignment.

Note down the details of GRN / TRS in the Raw material register (annexure –III) kept in Quality Control department and allocate an Analytical reference number in the allocated space for each batch/ lot of raw material by checking Mfg. Date, Exp. Date, Received Qty., GRN No. or TRS No., Manufacturer / supplier name against approved vendor list and compare the GRN as per party COA.

Check the GRN for all the details relevant to the sampling. Check the manufacturer’s COA received for acceptance criteria for individual test, manufacturing date, retest or expiry date. Also ensure that the material received is as per intended Pharmacopoeial grade (wherever applicable) and the manufacturer’s COA is as per current Pharmacopoeial requirement. Note the observations on the sampling checklist for sampling of Raw Materials. After checking, stamp the COA with blue ink as Verified By’ with sign and date as shown below:

VERIFIED BY “QC” Sign__________ Date__________  

In case of receipt of same batches of material repeated then perform only description, identification and water/LOD and remaining test shall be transcript from the previous lot of identical batch number.

The specification of concerned material is referred for the characteristic of the material e.g. light sensitive, temperature sensitive etc. storage conditions, pack description, necessary safety precautions and personal protective equipment to be used.

Prepare the sampled & under Test Labels and sampling kit with required sampling accessories and leave for sampling.

Check the consignment and GRN as per sampling check list as per Annexure II.

Use clean self sealing poly bags for collecting the solid raw material samples. Use clean and dried glass bottles for collecting the liquid raw materials.

Use sterilized glass bottles and spatulas for collecting the sample for microbiological analysis.

The consignment is stored in quarantine area with physical segregation with physical barrier. The consignment should be adequately segregated from other lots or batches.

The manufacturers / suppliers status label(s) (approved label) shall be defaced with “cross” marks, sign and date by store person.

The containers are clean and stored properly on pallets/racks.

The material shall not be exposed, in the case of damaged containers / packs. (If any).

Record any deviation on these points / or any other unusual observation in the sampling checklist and bring to the notice of the Head-Quality Control/ Designee immediately; perform sampling only after corrective action has been taken.

Check and verify for cleanliness of sampling room as per the checklist mentioned in Annexure V If found not cleaned get it cleaned before sampling.

Switch ‘ON’ the RLAF for at least 10 minutes, prior to Commencement of sampling activity. Record the details. Refer Annexure IV.

Check and record the details like Switch On time of LAF, differential pressure across the filters temperature/humidity of the area provided in cleaning checklist and line clearance of sampling room and usage record of sampling room as per Annexure V and Annexure IV.

In case of any deviation from the prescribed limit of the above inform engineering department and Quality Assurance and stop sampling till discrepancies are rectified.

Sampling chemist shall wear secondary gowning in the air lock and shall rinse the hands with 70% IPA before entering into the sampling room.

The workman shall bring the RM container near to the material air lock provided near the sampling room on a clean pellet.

Container shall be cleaned from outside before pushing inside the sampling room through the material air lock.

One clean container shall be taken at a time inside the sampling room through material entry air lock. After the completion of sampling from one container the same shall be taken outside. Take care that sampled and un-sampled containers are not mingled. Next clean container shall be taken inside the sampling room after the previous container is taken out one by one.

Open the containers under Sampling Booth (RLAF) only.

Use appropriate size of sampling device for sampling.

Use different sampling devices for different materials. In case any abnormalities found sampling devices shall be changed.

Follow the specific instruction as indicated on containers (if any) to be sampled.

For microbiological analysis sampling should be done separately using sterile equipments / accessories as required.

While calculating the quantity of the materials to be sampled refer the respective specification. Also consider the requirement of minimum sample withdrawal from individual container.   

For PL license related products 100 % sampling of active and inactive materials shall be carried out for identification purpose from each and every individual container. However √n + 1 sampling shall be followed if active and in active materials is coming from a single manufacturer or plant.

 Before reduce sampling (√n + 1) of incoming containers of active and inactive materials, sampling  chemist shall be ensure that the material was coming from single manufacturing plant as well as  directly from the manufacture. The same shall be verified with approved vendor list in which mentioned the provision for dedicated facility for single product manufacturer (Refer annexure – II, Sampling check list)  

In case contract giver (Other than PL license) sampling of active and inactive materials  shall be followed :

Case-1  Active and inactive materials, if the consignment is three or less than three containers then all containers are to be sampled and carried out complete analysis.

Case-2  In case the number of containers are more than 3 , then sampling to be done as per (√n + 1), where n = total number of containers. If the total calculated value is 20 then composition sample as per (√n + 1) then one composite sample shall be collected for complete analysis and identification shall be carried out from individual containers. in case calculated value is 21 of composition sample as per  (√n + 1) then the two composite sample shall be prepare for complete analysis and identification  shall be carried out from individual containers.

Whenever the total sampled quantity exceeds the required quantity as per specification (as explained above), reserve sample to be kept as per specification and the excess quantity to be included in the quantity for analysis, which is to be disposed off after completion of analysis.

For collection of reserve sample of raw material, collect the double quantity of required for one complete analysis. In case any microbiological test is also to be carried out in the sample, four times quantity of the material to be withdraw and keep in 4 different polybags (2 for chemical analysis and 2 for microbial analysis).

  • SAMPLING OF SOLID RAW  MATERIALS

To take the sample from the container by sampling equipment close the sampling pits by rotating the sampler.

Insert the sampler inside the container.

Rotate the sampler to expose the pits and agitate the sampler gently to & fro to fill the pits.

Rotate the sampler to close the pits & lift the sampler outside the container.

Hold the sampler in horizontal position on the butter paper & rotate the sampler so as to open the pits & collect the sample from the top, middle &   bottom portions of the container on the butter paper for visual observation like discoloration, lumps, non-characteristic odour, foreign matter, physical heterogeneity etc.

Simultaneously close the containers of the material sampled properly, with a cable tie for the inner bag and close the lid of the container.

In case of any abnormalities observed, inform to Head – QC/Designee for final decision.

In case there is no abnormality, mix the top, middle and bottom samples on the same butter paper to make a homogenous blend sample using spatula. Transfer the required quantity in a transparent self sealing poly bags by using a clean and dry spatula for identification test of each container.  After transferring the sample for identification test, remaining sample from the butter paper shall be transferred to the poly bag meant for composite sample as per sampling plan refer Annexure-VII.

  • Black polybag shall be used as an outer bag to enclose the sampled material in a plain poly bag. Label the polybag appropriately with the concerned test label i.e. Sample for identification, sample for composite analysis, sample for chemical analysis, sample for micro testing, sample control /retention sample refer – Annexure – I.

Likewise, sample the remaining individual containers and affix the label of “SAMPLED” to each container.

Weigh the required quantity from this composite sample for preparing Sample for analysis and control sample.

For the microbiological sampling, the sampling activity has to be carried out in sterilized glass bottle by the sterilized spatula.

Discard the used butter paper in the waste bin.

SAMPLING OF LIQUID RAW MATERIALS

FROM LARGE CONTAINERS (SOLVENTS)

Follow the step mentioned and prepare the sampling kit with glass sampler.

Liquids from large containers shall be sampled in the solvent sampling and Dispensing room.

Insert the Glass sampler in the container and withdraw the sample.

 If the containers are more than 20 nos. in a consignment, one composite sample collected from each set of 20 containers as per Annexure-VII.

 If the containers are less than 20 in a consignment, only one composite sample shall be prepared from individual pooled sample for complete analysis. 

Take the required quantity for composite sample and for identification from individual container.

Simultaneously close the containers properly.

Likewise sample the remaining individual containers.

FROM SMALL CONTAINERS

Mix the content of the liquid container well by shaking the container and sample. Insert the pipette in the container and with the help of the rubber bulb withdraw the sample.

Take the required quantity for composite sample and for identification from individual container.

Simultaneously close the containers properly.

Likewise sample the remaining individual containers.

Mix the liquid quantities from the individual containers well to prepare composite sample.

Fill the liquid in the sampling bottle(s).

Label the sample bottles appropriately with, Sample for identification test / Sample for analysis / Sample for microbiological analysis (If required).

After sampling affix label of “SAMPLED” to sampled container.

 Put the liquid sampler after use in a polybag and tie with plastic rope appropriately labeled and transfer to washing area for cleaning.

On completion of sampling, keep the sampled container their appropriate storage conditions and in designated area, securely reseal the opened container and affix the duly signed ‘Under Test’ “0 / -“ numbered label on consignment card.

Affix the duly signed ‘Under Test’ label on each and every container of the batch in a position preferably just below the product label / manufacturer’s label on the container. If not possible, affix it at the side of manufacturer’s label. Proceed in the same manner for the rest of the containers.

For containers where sticker labels cannot be affixed, stick the labels on cardboards and tie them to the containers.

After sampling, the used sampling equipment should be placed in self sealing polythene bag (to avoid spillage and cross contamination) with a label “To be cleaned” and should be taken in the sampling kit / polythene bags to the washing area of warehouse.

After completion of sampling, clean the sampling area as per the cleaning procedure. Cleaning of sampling room to be done after sampling of each batch. Fill the checklist of cleaning and line clearance of sampling room after each sampling. Refer Annexure V.

Bring the samples to the laboratory and keep them in the place designated for them. The sample should be stored as per storage condition specified in individual specification and should be preserved their appropriate storage conditions ,In case of microbiological samples arrange to sent for testing promptly.

Indicate the container number on the ‘Sample for Analysis’ label affixed on the polythene bag/sample bottle as per container number specified on “Under Test label”. In case of printed sample for analysis label, ensure that the container number on Under Test label tallies with the container number on “Sample for analysis” label affixed on polythene bag/sample bottle. Proceed in the same manner for the rest of the containers.

Carry out the sampling of Raw Materials as detailed in this document. The consignment should be sampled preferably within 15 days of receipt of GRNs.

Enter the sampler’s name, Sampling date and no. of samples in GRN.

Material shall be stored at their appropriate storage condition for e.g.at 20 to 25° C, at 2 – 8° C / or in a deep freezer and ambient temperature and allow the material to attain the room temperature before doing the sampling.

Whenever the liquid material is received in the drum, affix the status label on the drum in such a way that it will not get soiled while dispensing or affix the same on the cardboards and tie them to the air leak hole of the drum.

In case of sensitive materials (e.g. thermal labile, highly oxidative etc), or costly materials, separate “QC Sample pack” should be demanded from manufacturer along with consignment and sampling from consignment should be avoided.

API and excipients coming from single product manufacturing facility and coming directly from the manufacturer can be allowed for reduced sampling after approval from QA (Refer Annexure-II).

Arrange for the cleaning of the sampling accessories and the proper storage of the sampling and safety accessories with status label. ‘Cleaned’.

Sampling for Re-test

Check the details on the Test Requisition Slip (TRS) and make the entries in the checklist for sampling of Raw material. Refer Annexure II.

In case the Test Requisition Slip for Retest, withdraw the sample quantity required for re-analysis testing.

Deface the Approved label and paste the ‘Quarantined for Reanalysis’ labels on the Approved label of each container with sign and date.

Follow procedure for sampling same as initial sampling procedure.

Affix the duly signed under test label just below the earlier defaced status label as far as possible with respect to the size of the consignment.

Note:

1) Ensure that the earlier Passed labels are defaced and should be signed and dated by the  store person.

2) Ensure that the retest materials shall be shifted in the quarantine area with proper segregation.

  • Sampling of consignments received on Stock Transfer Memo

Check the details on the sampling intimation documents GRN and make the entries in the sampling checklist. Refer annexure II.

Follow procedure for sampling same as initial sampling procedure.

Withdraw the sample quantity required for analysis as per specification. Check if all the tests mentioned in the Certificate of analysis of source unit are as per specification and if any test is not performed, then withdraw the quantity of samples required for that test also.

Affix the duly signed ‘Under Test’ label just below the earlier defaced status label of transferring unit as far as possible with respect to the size of the consignment

  • TRAINING :

As per Employee Training SOP

  • DISTRIBUTION :

As per SOP on SOP

  • ANNEXURE:

Annexure-I      : Labels for Raw Materials

Annexure-II    : Checklist for sampling of raw materials

Annexure-III   : Raw Material Register                                          .

Annexure-IV   : Area cleaning and usage record of sampling room  

Annexure – V : Checklist for cleaning and line clearance of sampling room

Annexure – VI            : Flow diagram for sampling

Annexure –VII: Table for Propositions of composite samples.

Annexure –VIII: List of materials from biological origin

  • REFERENCES(S):

Eudralex-Annex-8: Sampling of Starting Material and part-1 chapter 6: Quality Control

SOP On Daily Work Plan

The purpose of this SOP is to lay down a procedure describes the daily work plan of the laboratory.

This SOP is applicable to routine and non-routine functions in Quality Control Department at manufacturing facility of Pharmaceutical Industry.

  • PROCEDURE:

Work shall be allotted to analyst for the day by the Section / Department Head, including the work completed and work pending in daily work plan.

Obtain the green data sheet from the Section Head for the samples to be tested except in the case of all types of samples.

At least twice during the day check and record the temperature and humidity, as applicable, of the main laboratory and instrument room. Make the entries in humidity record, and temperature record for reserve sample room. If the temperature is not within the limit as specified in individual form, immediately inform the engineering department and unit Q.A. for corrective action. Every morning carry out the calibration of the pH meter, and carry out the self calibration of the electronic analytical balance.

Carry out the sampling and testing activities and any other assigned work strictly according to the documented procedures, unless otherwise authorized by the Department Head.

Prepare the composite and reserve samples during sampling and carrying out the tests.  Keep the reserve samples in the designated place after making relevant entries in the reserve sample register.

Enter the weights, titers and other observations directly on the Raw data sheet as and when the tests are performed.

Bring to the notice of the Section Head any difficulties faced in carrying out the tests or any unusual observations made either on the samples or in the results of the tests.

Check all the raw data and the results against the specifications and trends (wherever applicable). Dispose off the remaining analytical sample after getting the report checked by the Section Head.

Keep the intimation slip (e.g. GRN, Test Request Slip etc), in the appropriate files or folders, which have been provided, and not on the workbenches, except when they are in use.

After the COA has been approved, file the completed reports in the respective files.

Prepare the appropriate status labels and affix them on the consignments of Raw materials/ Packing materials.

Leave the work place clean after testing is over. Put away the used glassware for washing and put back the specifications on the shelves.

At the end of the day hand over the folder with the completed Test data sheets and other papers to the Head-QC/designee.

Review the Raw data sheets and works of the individual analysts for the previous day’s work and allocate the work for the day to them, on the basis of priorities related to production requirements and any other emergencies.

Discuss promptly with the Department Head if any difficulty experienced in carrying out a test or any result deviating from the specification and take remedial action.

Discuss with the Department Head for any investigation to be done on “OOS” results and prepare report on such an investigation.  As a part of investigation, carry out retesting for the same sample.  In some cases, if required, resampling can be done.

Carry out analysis of samples, particularly of those involving complex tests or requiring confirmation of doubtful results.

Scrutinize the completeness of A.R. register, Schedule/Programme in order to see if they are up-to-date.

  • TRAINING:

As per Employee Training SOP

  • DISTRIBUTION:

As per SOP ON SOP

  • ANNEXURE:

Annexure I : Daily work Plan

  • REFERENCES(S):

              Nil

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 Job Responsibility

The purpose of this Standard Operating Procedure (SOP) is to lay down the procedure for defining job responsibilities of individuals.

  1. Objective :

The purpose of this Standard Operating Procedure (SOP) is to lay down the procedure for defining job responsibilities of individuals.

  • Scope :

This SOP is applicable to all responsible persons of pharmaceutical Industry       

  • Responsibility:

Officer QA – shall prepare the SOP co-ordination with all respective departments shall be responsible for Preparation of SOP.  

Executive QA / designee shall review the SOP,

Head Quality Assurance shall approve the SOP.

  • Procedure:

To maintain a satisfactory system of QA and manufacturing of drug product, as per cGMP requirement.

Each department shall be provided with defined responsibility to perform the task for manufacturing of the Drug Product to meet cGMP requirement.

The duties of each department are defined but not necessarily be limited to as follows.

Warehouse:

Preparation and review of the instruction for describing the receipt, identification, quarantine, storage and handling of raw materials/ Packing materials/ Finished product.

Receipt, identification, quarantine, storage and handling of material / product according to pre approved instructions.

Environmental monitoring of the area as per predefined procedures.

Making sure that any deviation is reported and investigated properly.

Making sure that storage area is cleaned.

Inventory control

Production

Preparing and reviewing the instructions for the production of products according to written procedures.

Producing products according to pre-approved instructions.

Reviewing all production batch records and ensuring that are completed and signed.

Making sure that all production deviations are reported and evaluated and that critical deviations are investigated and conclusions are recorded.

Making sure those productions facilities are clean and disinfected when appropriate.

Making sure that the necessary calibrations are performed and recorded in respective areas.

Making sure that the premises and equipment are maintained and recorded in respective areas.

Making sure that validation protocols and reports are prepared and reviewed.

Evaluation of proposed changes in product, process or equipment.

Making sure that new and when appropriate, modified facilities and equipment are qualified.

Engineering

Preparation and review of the instruction for describing the procedure for preventive maintenance, breakdown maintenance.

Evaluating any change in equipment, machinery.

Calibration of equipment and instrument used in manufacturing.

Operation of all Utilities like Water, HVAC, Boiler, Compressed Air etc.

Execution of Installation and Operational Qualification of equipment as per approved protocol.

Quality Control

Sampling/testing and release of incoming, in process and finished product as per the laid down specifications and standard testing procedures.

Release / Reject of raw material / Packing Material/Finished Product.

Making sure that critical deviations are investigated and resolved.

Out of Specification Investigation.

Preparation and Standardization of volumetric solutions and reagents.

Inventory control of chemicals / Glassware / media etc.

Preparation and review of all SOP’s related to department, Specification and test procedures.

Initiation and review of any change related to the department.

Preparation and execution of validation protocol for method validation and Analyst validation.

Making sure that materials are appropriately tested and results are reported.

To conduct Stability Studies.

Calibration of instruments used in the Laboratories.

Handling of Reference standard and Working standard and qualification of working standard.

Quality Assurance

To ensure that Quality systems are maintained as per cGMP requirement.

Review of batch records and release of Finished Product.

Approval of all SOP’s, STP’s, Specifications and master processing records etc.

Making sure that all critical deviations are investigated and resolved.

To conduct Self Inspection and to conduct Vendor Evaluation.

Change Control review and Approval.

Review and Approval of all validation related activities.

Performing Product Quality review.

Handling and Investigation of Market Complaints and product recall.

Human Resource

To prepare procedure for personnel hygiene medical checkup, housekeeping.

Employee Welfare.

To coordinate for training to all employees.

To conduct regular medical checkups and house keeping

The department head shall ensure that adequate number of personnel with necessary qualification and experience are provided to complete the departmental responsibility. Department Head shall prepare job responsibility of every employee working in their department and shall explain the same to employee.

  • TRAINING:

As per Employee Training SOP

  • DISTRIBUTION:

         ANNEXURE:

Annexure-I                           :  Format for Job Responsibility

  • REFERENCES:

NiL

SOP on Preparation of Culture Dilution

The Purpose of this SOP to lay down the procedure for preparation of Culture dilutions.

This procedure is applicable for Culture Maintenance in the Microbiology Laboratory at Pharmaceutical Manufacturing Industry.

PROCEDURE

Serial Dilution

 For the purpose of preparing appropriate microorganism from the weekly- transferred working culture slant, inoculate a loopful of culture to 10 ml of Nutrient Agar for Bacteria & Fungi.
 Incubate the bacterial suspension at 32.5 ± 2.5°C for 24 to 48 hours & fungal suspension at 22.5 ± 2.5°C for 24 to 72 hours for enrichment.
Serially dilute the enriched suspension in 0.9% sterile saline solution in a ratio of 1: 10 dilution by transferring as follows.

Transfer the culture suspension in a sterile test tube.

Collect the suspension in a sterile test tube.

Vortex the culture suspension to obtain a uniform suspension.

Carry out serial dilution so as to obtain a culture suspension of 10-100 cfu/ml by     following the steps given below.

                Transfer 1 ml of the suspension to 9 ml sterile normal saline solution – 101    Dilution.

1 ml of 101 Dilution to 9 ml sterile normal saline solution – 102 Dilution.

    1 ml of 102 Dilution to 9 ml sterile normal saline solution – 103 Dilution.

    1 ml of 103 Dilution to 9 ml sterile normal saline solution – 104 Dilution.

    1 ml of 104 Dilution to 9 ml sterile normal saline solution – 105 Dilution.

    1 ml of 105 Dilution to 9 ml sterile normal saline solution – 106 Dilution.

    1 ml of 105 Di Dilution to 9 ml sterile normal saline solution – 107 Dilution.

Check the CFU/ml from the above-prepared dilutions by transferring 1 ml of the inoculum on Nutrient agar plate for Bacteria & Fungi by pour plate method. Incubate the plates for 18 to 24 hours at respective Temperature as mentioned above.
On observation of visible microbial growth on each plate, count & record the average number of CFU in Preparation of culture suspension register. Count the CFU/ml from each Dilution & select the dilution tube which gives 10-100 CFU/ml. Store the same Tube for daily use of Culture for Positive Control. Record all Dilutions Result In annexure. Use it for one week & discard (from date of preparation) as per SOP for disposal of media and record in the format.
Take 1 ml of the above prepared culture suspension for Positive control for environmental monitoring, MLT and fertility test.

Abbreviations :

CFU: Colony Forming Unit
MLT: Microbial Limit Test
NaCl: Sodium Chloride

Training :

As per employee training SOP.

Annexure :

Annexure I: Culture suspension preparation Record

Annexure II : Culture Suspension Usage Record

SOP on Microbial Testing of Drain Water

The Purpose of this SOP is To lay down the procedure for Microbial testing of drain water in the production area of the Pharmaceutical Manufacturing Site.

This SOP is applicable to describe the procedure of Drain monitoring Microbial Contamination for Production area and microbiology lab at of Pharmaceutical Manufacturing Site.

PROCEDURE

All drains in the production area shall be checked to monitor the effectiveness of cleaning and disinfecting agents once a month.
Sample 100 ml of drain water from each drain and collect it in a sterile glass container with the help of previously sterilized pipette.
 Following tests shall be performed on the drain water collected:


a) Total Microbial Count.
b) Absence of Pathogens.


 Filter the sampled drain water through 0.45 membrane filter.
For Phenolic disinfectants, dilution of drain water with sterile distilled water and filtration through 0.45 micron is sufficient. However, whenever other types of disinfectants.
Wash the filter paper 2 times with sterile Normal Saline 50 ml 1st time and 50 ml Second.
Inoculate the filter paper in 100 ml of Normal Saline.
Shake thoroughly (so that the contents of filter paper comes in Normal Saline).
Perform the Total Microbial Count and test for absence of Pathogens as per the standard.

Count and record the results in Drain Water (Microbiological Testing) Record.
Necessary feedback shall be given to Production for corrective action if required.

Frequency: Monthly

Acceptance Criteria:

For Bacteria 1000 CFU/ plate

For Fungi 100 CFU/Plate

Training:

Training is as per Training SOP

Annexure :

Annexure I: Microbial Testing of Drain water Logbook

Annexure II: Microbial Testing of Drain Water Report

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.