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

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