Raw Material Sampling Procedure-API & Excipient

Standard Operating Procedure (SOP) and Guideline for sampling of raw material (API and Excipient) / Starting material for analysis.

Raw Material Sampling Procedure

1.0   Objective :

• • To lay down a procedure for sampling of raw materials.

2.0   Scope :

• • This SOP is applicable for sampling of raw materials at pharmaceutical drug manufacturing plant.       

3.0   Procedure :

• • Stores shall submit the Good Receipt Note to QC department and RM Section Head/Designee shall enter the GRN details in raw material inward register as per Annexure-IV.

• • After the planning of sampling of raw materials, send the GRN to QC sampling area as per priority of material.

• • QC chemist shall receive the Goods Receipt Note and shall ensure that the consignment is placed in quarantine area, batch wise on pallets.

• • Ensure that the containers are clean.

• • Ensure that the QUARANTINE label is affixed on each container.

• • QC chemist shall print the “UNDER TEST” label and shall sign and affix duly checked labels on each container of consignment.

• • QC chemist shall cross the approved vendor status label after affixing the under test label.

• • After review of above points, Chemist QC shall fill the Annexure-I “Raw material Sampling Record”.

• • If any discrepancy observed during verification of materials, information shall be given to Head QC and Head QA/Designee for necessary action.

• • Preparations for Raw Material sampling:

• • Availability of clean sampling tools.

• • Availability of over gown, trouser, snood, hand gloves and shoes cover etc.

• • Temperature and relative humidity of area is within limit.

• • Pressure differential of areas are within limits.

• • Proper functioning of RLAF.

• • Area and RLAF is clean and records are maintained.

• • Calibration of balance.

• • Trolley for movement of containers.

• • Availability of SAMPLED labels.

• • Prepare the labels for the samples as per respective sop for labeling.

• • • Identification Sample

• • • Composite Sample

• • • Pool Sample

• • • Microbial Sample

• • • Reserve Sample

• • QC Chemist shall enter the consignment details in Annexure-I.

• • Sampling Plan:

• • For API: The sampling shall be done from all containers (100%).

• • For Excipients: The sampling shall be done from √n + 1container, where n is number of containers received in the particular batch number.

Sampling from 3 Layers.

• • For Vitamin A, Vitamin E and Vitamin D3, sampling from one container shall be done.

• • Nitrogen purging shall be done before closing the sampled container.

• • For Sugar, sampling from five bags shall be done under portable LAF, placed in sugar storage area.

• • Sample Quantity (Raw Material Sampling):

• • QC Chemist shall draw the sample quantity as defined in “List of Raw Material with Sample Quantity” Annexure-II for each test and record the details in “Raw Material Sampling Record” as per Annexure-I.

• • For new raw material sampling, section head shall intimate the QC chemist for sample quantity and same shall be updated in addendum as per Annexure-V.

• • “List of Raw Material with Sample Quantity” Annexure II shall be updated after 06 months or whenever required as per “Addendum for Raw Material with Sample Quantity” Annexure-V.

• • The sample quantity is divided in two parts as follows:

  • 1^st part is for analysis and 2^nd part is for reserve sample, which should be twice the quantity required for one complete analysis except the quantity required for microbiological analysis (if applicable).

• • For the active pharmaceuticals ingredients where the single identification is carried out for individual containers and other identification test shall be carried out on pooled sample.

• For Active pharmaceutical Ingredients (API) – Sampling of Raw Material:

• • Draw approximately sample for identification purpose from each container as per the quantities mentioned in Annexure-II.

• • Note: If any consignment of  existing vendor get rejected in Assay, Related substances or LOD/water, then subsequent three consignments shall be sampled from top, middle, bottom of each container,

• • Prepare the pool sample and perform respective test as failed in the previous consignment.

• • For new vendor consignment shall be sampled from top, middle, bottom of each container prepare the pool sample and perform the entire test mentioned in respective STP for first three batches.

• • QC Head/Designee shall inform sampling chemist to perform above activity.

• • For Assay and Water Content/LOD:

• • Composite the sample ensuring that from each sampled container, approximately equal quantity, is taken for composite sample.

• • Such composite sample shall not represent more than 25 sampled units.

• • If sampled units are more than 25, make subsequent composite sample in multiple of units i.e.

• • Continue in similar way for every 25 containers, or part thereof.

• • Prepare a pooled sample by taking equal quantity from all composite samples.

• • Carry out the assay and water/LOD for all composite samples prepared as above and report average result

• • Perform complete analysis on pooled sample expect Assay and LOD water test.

• • For the component, having microbial test, QC chemist shall collect the sample.

• • Depending on the nature of the material and ease of collection, samples are collected either in polybags, glass bottles or PET bottles.

• For Excipients – Sampling of Raw Material:

• • Total sample quantity drawn as mentioned in Annexure-II and recorded in “Sampling Record” as per Annexure-I.

• • The sample quantity described in Annexure–II “Raw Material Sample Quantity and total quantity required for analysis and reserve sample or control sample purpose.

• • Analyst shall collect the sample from each container in such a way that approximately equal quantity is taken from each sampled container and total sample quantity should be same as described in Annexure–II.

• • The sample quantity is divided in two parts as follows:

• • 1^st part is for analysis 

• • 2^nd part is for Reserve sample or control sample, which should be twice the quantity, required for one compete analysis except the only required for microbiological analysis (if applicable).

• • For the analysis: Perform the complete analysis on pooled sample and the test of identification should be carried out over the pooled sample with all the tests under the test of identification.

• • For the component, having microbial test, QC chemist shall collect the sample.

• Retesting of Raw Materials:

• • Retest material sampling shall be done as per procedure defined above.

• • Retest period and sample quantity for re-testing is defined in Annexure-II.

• • The Material which are due for retest shall be retested as per specification prior to use in manufacturing.

• Sampling Aids – Raw Material Sampling :

• • Stainless steel (SS) sampling rod

• • Glass sampling rod

• • Spatula/Spoon/Scoop/Pointed scoop

• • Glass pipette

• • Liquid sampler

• • Bubbler

• • Sampling bottles/poly bags

• • Opener, Cutter and Scissors

• • Cable tie

• Procedure to withdraw samples – Raw Material Sampling :

• • Inspection of Raw Material Sampling Aids :

• • If found any scratch in sampling aids like Spatula, Spoon, Sampling rod etc. shall be replaced with new.

• Sampling Procedure of Solvents/Liquids in Solvent Dispensing/Sampling Area:

• • Liquids (as Sorbitol 70%, Liquid glucose, Glycerin, Polyethylene glycol, etc…).

• • If containers are more than 50kg weight.

• • Liquid container shall be brought and placed under vertical LAF in dispensing/sampling area.

• • Take clean, dried and individually wrapped sampler for sampling.

• • Open the unit to be sampled, carefully with the help of suitable opening devices.

• • Withdraw the quantity of sample in suitable container as described in Annexure-II.

• • Label the sampled container with ‘SAMPLED’ label and sign it and assign number 1 for first sampled unit and thereafter.

• • Label the composite sample with RAW MATERIAL SAMPLE (COMPOSITE) label and sign it.

• • After sampling close the each sampled container properly.

• • After sampling transfer the sampled container in under test area.

• • Record the sampling details in sampling Logbooks of respective area.

• • Wrap the used sampling aids with poly bags and transfer for cleaning.

• • Send sample for analysis to the QC Laboratory.

• • Inflammable solvents Sampling :

• • Inflammable solvents container shall be brought with the help of drum trolley (available in Solvent Storage area) in entry of inflammable solvents air lock area provided in Raw material store for cleaning of solvent drums.

• • Place the cleaned solvent drums under vertical LAF and follow the sampling procedure.

• • After sampling close the lid of drum tightly & transfer to solvent storage area.

• • Note: Control sample of Liquid sample, solvent and flammable material, Sodium Hydroxide, Vitamin D3, Cyanocobalamin, Mecobalamin and Sucrose should not be kept.

• • Sampling of liquid glucose shall be done by spoon / Spatula from upper layer.

• • Sampling Procedure for solid/Liquid material below 50kg container:

• • On the day of sampling, Chemist QC shall start the AHU of sampling area(s).

• • If temperature & relative humidity is within the limit, proceed for the sampling activity.

• • In case temperature/relative humidity is not within the limit, wait till the required temperature/relative humidity is achieved.

• • Start the sampling activity, only after getting the required temperature and humidity.

• • Switch on the RLAF following respective SOP .

• • Arrange all the containers on the pallet. During sampling ensure that sampling is done in such a way that the sample is representing the whole lot.

• • Transfer the material with trolley to the material air lock (Sampling Room).

• • Ensure that the area under RLAF is clean.

• • Only one container/bag shall be taken under the RLAF sampling booth.

• • Take clean, dry and individually wrapped sampler for sampling.

• • Open the container/bag to be sampled, carefully, with the help of suitable opening devices.

• • Withdraw the sample quantity of sample in suitable containers /poly bags/bottle for microbiology sample.

• • Clean the sampler after sampling of each container/bag with cotton cloth

• • Label the sampled container/bag with ‘SAMPLED’ label and sign it and assign number 1 for first sampled container/bag and thereafter.

• • Label the identification sample, composite sample, pool sample, microbial sample, reserve sample and sign it.

• • After sampling close the each sampled container/bag properly.

• • After completion of sampling, switch off the RLAF.

• • Clean the sampling area and record the details in the sampling of raw material log book as per Annexure–III.

• • Sampled container/bags are returned to the Under Test Area.

• • Wrap the used sampling aids in polybags and transfer for cleaning.

• • Send sample for analysis to the QC Laboratory.

• • Clean the sampling tools.

• • Clean the sampling area and RLAF.

• Use of door interlocking system – Raw Material Sampling:

  • Check the door interlocking system, it should be functional i.e red indicator glow.

• • Press the push button, green indicator glow.

• • Open the door and place the material in the air lock and take out the material from the air lock.

• • Leave the door and let it closed.

• • Do not press emergency button unless required.

• • If the red indicator does not glow check the other door of the air lock for proper closing.

• • Ensure that one Raw material is taken for sampling in room at one time and only one container of Raw material is taken under RLAF.

• • Follow safety instructions, mentioned on “Material Safety Data Sheet”.

• • During sampling of liquid materials, if the sampling rod (glass) gets broken, then reject the container being sampled and inform to QA and Head Store. Affix a label stating as “Rejected”.

• • Sampling of light sensitive products, sampling shall be performed only under sodium lamp. After sampling store the sample container in black poly bag.

  • Wear the snood and hand gloves during sampling.

• • Switch on the RLAF 30 minutes before starting the sampling.

• • QC Chemist shall change the Gowning, Gloves, Shoe cover, Cap and snood, for sampling different APIs.

• • Composite sample quantity shall be as per retest sample quantity.

• • Ensure that container should be inside the “Safe Zone” of RLAF.

• • The Analyst drawing the sample should ensure that he/she stands on the side of container, thereby avoiding obstruction of airflow current, to the container being sampled.

• • The active pharmaceutical ingredient having EDQM grade materials shall be checked that the received material is of EDQM CEP approved and have the certificate of suitability (COS) number which should be verified in the EDQM website against the material received.

• • Sterile utensils shall be used for sampling of microbiological testing.

• • Utensils shall be sterile as per SOP.

• • Sample for microbiological analysis shall be collected in sterile polybag / container.

• • The sample for microbiological testing shall be collected prior to chemical testing sample from the upper layer of container following √n + 1

4.0   Reference :

• • In-house

• • The Rules Governing Medicinal Products in the European Union: Volume 4, EUGMP

• • Medicinal Products for Human and Veterinary GMP Part I Chapter 6. Quality Control

5.0   Annexure – Sampling of Raw Material :

Annexure –I : Raw Material Sampling Record.

Annexure – II : List of Raw materials with sample quantity.

Annexure–III : Sampling Log-Book for Raw material.

Annexure-IV : Raw Material Sampling Inward Register.

Annexure- V : Addendum for Raw Materials with Sample Quantity.

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