SOP for Sampling of Granules (Blends), Uncoated Tablets, Coated Tablets and Finished Product

1.0 OBJECTIVE:

The objective of this standard operating procedure (SOP) is to lay down the procedure for sampling of Granules (Blend) / Uncoated Tablets / Coated Tablets / Capsules and Finished product at various stages of manufacturing and packing of drug product.

2.0 SCOPE:

The scope of this SOP is to provide the procedure for sampling of Granules (Blend) / Uncoated Tablets / Coated Tablets / Capsules / Finished product for products manufactured at [company name].

3.0 RESPONSIBILITY:

IPQA: Sampling of Granules (Blend) / Uncoated Tablet / Coated Tablets / Capsules / Finished product.

Production: To coordinate IPQA person for sampling of the  

Granules (Blend)/ uncoated tablets/ coated tablets / Capsules / Finished product. 

4.0 PROCEDURE

4.1 General Instruction to be followed for Sampling of Granules (Blend), uncoated and coated tablets, capsules and finish product. 

4.1.1 Sampling activity shall be performed wearing protective clothing like hand gloves, mask and secondary gowning during manufacturing process.  

4.1.2 Use clean, dry stainless steel spatula, spoon and sampling rod for sampling Granules (Blend). 

4.1.3 Store sampling tools in clean area wrapped in clean poly bags. 

4.1.4 Check that the quality of the sample and the product being sampled is not affected by the sampling activity. 

4.1.5 Check that the sample and materials being sampled are protected from external contaminants. 

4.1.6 Check that sampling activity is carried out in such a way so that the spillage of material is minimum.

4.1.7 Do not place sampling tools on the floor.

4.1.8 If any abnormalities are observed at the time of sampling stop sampling activity. Immediately intimate Head-Production and Head-QA for further investigation.

4.2 General Instruction to be followed for Sampling of Finished Product.

4.2.1 Check to sample the product from different stages so as to take the sample as representative of the batch. 

4.2.2 The samples collected shall be placed in secure place to avoid the product mix up. 

4.3 Sampling of Granules (Blend) (Dry mix, wet mixing, Dried granules, Premixing granules, pre lubricated granules and lubricated granules): 

4.3.1 Production personnel shall intimate IPQA person to collect sample through Product intimation slip as per Annexure – I.

4.3.2 IPQA person shall Check the following before withdrawing samples from the batch, 

4.3.3 Collect self-sealing polybags, sampling rod (in case of Validation), spoons, spatula, hand gloves, SS container etc. 

4.3.4 IPQA person shall prepare the label for sample for analysis as per Annexure – II with respect to the written intimation mentioning the product name, batch number, batch size, manufacturing date, expiry date, stage etc.Incase of validation the sticker label for sample for analysis as per annexure –VI shall be prepared for each particular location.

4.3.5 IPQA person will carry product intimation slip along with the other requirements as mention above in sample kit.

4.3.6 IPQA person will Check that the respective stage of the process is completed and BMR is filled up to that stage.

4.3.7 Check correct label with product details and stage of operation.

4.3.8 To check the correct status labelling on the equipment / IPC as per product intimation slip. (Product name, B.No, stage etc.)

4.3.9 In case of validation / optimisation / submission batches. Sampling of samples may be done after Dry mixing, Binder solution, Wet mixing, Dried Granules (Blend), Premixing, Prelubrication and Lubrication as per details given in protocol. 

4.3.10 In case of binder solution / paste sampling the samples shall be done as per the respective protocol.

4.3.11 Collect the granules / blend from different locations of the equipment and sample quantity as per protocol during sampling of lubricated granules / blend with the help of sampling devices in double fresh self-sealing poly bag.  

4.3.12 In case of batches other than validation / optimisation / submission batches, Check bin / intermediate product container (IPC) containing lubricated granules are labelled properly. Verify the label of bin / IPC / HDPE against the (BMR) and product intimation slip. Collect the granules (Blend) from different IPC / bin / HDPE with the help of cleaned spatula and store in a fresh self-sealing poly bag as composite sample as per quantity mentioned in Annexure III. 

4.3.13 Collect granules (Blend) from at least five different locations of one IPC / bin / HDPE if a granule of the entire batch is stored in a single IPC / bin / HDPE as per quantity mentioned in Annexure III.

4.3.14 Prepare a composite sample for checking loss on drying (LOD) in IPQA OR send sample for QC laboratories and appearance of granules (Blend).(in case of validation) 

4.3.15 If sample collected for validation / optimisation / submission batches sample quantity shall be collected as per the sampling plan in protocol and the test shall be performed as per protocol. 

4.3.16 In case samples are required to be analysed from different locations of the equipment, collect samples separately and label them accordingly as per the protocol.

4.3.17 Label the self sealing poly bag containing sample for LOD verification in IPQA laboratory and affix (Sample For Analysis label) indicating Product Name, Batch No., Batch Size, Manufacturing Date, Expiry Date, Sampled by, Sampled quantity, Sampling Date on the outer surface of the inner self sealing poly bag containing sample.  

4.3.18 Record the details of sample collected in the sampling detail register as per Annexure-IV.

4.3.19 IPQA person affix yellow colour UNDER TEST label (as per SOP No. SOP/TAB/046) on all containers from which the samples are collected. 

4.3.20 IPQA person / QC Laboratory analyse the granules as per specification and enter the values in controlled worksheet copy.

4.3.21 After verifying the report by second IPQA person, the IPQA person affix green colour “APPROVED” label (as per SOP No. SOP/TAB/046) on all containers.

4.3.22 Destroy the remaining quantity of granules and enter the details in sample destruction logbook as per Annexure – V.

4.3.23 IPQA person will monitor the cleaning of sampling devices with purified water. Allow the sampling devices to air dry. Wrap the sampling devices in polythene bag and store in a dedicated area.

4.4 Sampling of Uncoated Tablets: 

4.4.1 IPQA person shall check the following before withdrawing samples from the batch.

4.4.2 Collect polybags, hand gloves etc.

4.4.3 IPQA person shall prepare the label for sample for analysis mentioning the product name, batch number, batch size, manufacturing date, expiry date, stage etc.

4.4.4 IPQA person will carry the requirements as mention above in sample kit.

4.4.5 During the manufacturing process the IPQA person goes to processing area.

4.4.6 Wear hand gloves and secondary gown as per the procedure.

4.4.7 Check that the respective stage of the process is ongoing and BMR is filled up to the current stage.

4.4.8 Check that the correct labelling is done with required details and stage of operation on the equipment / IPC / HDPE container (Product name, B.No, sampling stage etc).

4.4.9 Collect the samples for in process checks as per specification and frequency mentioned in respective BMR. Collect samples in slightly more quantity in SS container & label it accordingly. SS container shall be stored in IPQA department.  

4.4.10 In case of validation / optimisation / submission batches: Collect the uncoated tablets at different intervals of time, speed and sample quantity as per protocol in double fresh self-sealing poly bag.  

4.4.11 Label the self-sealing poly bag, containing sample for in process checks with white “Sample For Analysis” label. 

4.4.12 Perform in process checks in IPQA department and store part quantity of sample for QC analysis in S. S. container with status label.

4.4.13 At the end of the process production person gives product intimation slip.

4.4.14 The IPQA person Checks that the BMR is completed till the current stage and also check the correctness of labelling on the plastic container with respect to product intimation slip.

4.4.15 IPQA person prepares composite sample from the left over samples collected during in process checks, and collect the quantity of sample as per annexure III in double polybags and affix.

4.4.16 Label (Sample For Analysis) indicating Product Name, Batch No., Batch Size, Manufacturing Date, Expiry Date, Sampled by, Sampled quantity, Sampling Date is kept on the outer surface of the inner self sealing poly bag containing sample for analysis in QC laboratory. 

4.4.17 Record the details of sample collected in the sampling detail register Annexure-IV.

4.4.18 Send the composite sample to QC in sample kit with the product intimation slip and sampling details register for acknowledgement of sample receipt and subsequent analysis. IPQA person affixes yellow colour “UNDER TEST” label (as per SOP No. SOP/TAB/046) on all intermediate process / HDPE containers from which the samples were collected.

4.4.19 Take composite sample quantity for in process as per Annexure – III in IPQA laboratory. 

4.4.20 IPQA person perform the in process as per specification and enter the values in controlled worksheet copy / BMR.

4.4.21 Destroy the remaining quantity of core tablets and enter the details in sample destruction logbook as per Annexure – V.

4.4.22 After receiving the analysis report from QC laboratory and getting it verified by QA head or his designee the IPQA person Checks that the analysis of the product passes. After conformation, IPQA person affix green colour “APPROVED” label as per (as per SOP No. SOP/TAB/046) on all intermediate process containers or HDPE container.

4.5 Sampling Of Capsules: 

4.5.1 IPQA person shall Check the following before withdrawing samples from the batch:

4.5.2 Collect polybags, hand gloves etc.

4.5.3 IPQA person shall prepare the label for sample for analysis mentioning the product name, batch number, batch size, manufacturing date, expiry date, stage etc.

4.5.4 IPQA person will carry the requirements as mention above in sample kit.

4.5.5 During the manufacturing process the IPQA person goes to processing area.

4.5.6 Wear hand gloves and secondary gown as per the procedure.

4.5.7 Check that the respective stage of the process is ongoing and BMR is filled up to the current stage.

4.5.8 Check that the correct labelling is done with required details and stage of operation on the equipment / IPC / HDPE container (Product name, B.No., sampling stage etc).

4.5.9 Collect the samples for in process checks as per specification and frequency mentioned in respective BMR. Collect samples in slightly more quantity in SS container & label it accordingly. SS container shall be stored in IPQA department.  

4.5.10 In case of validation / optimisation / submission batches: Collect the Capsules at different intervals of time, speed and sample quantity as per protocol in double fresh self-sealing poly bag.  

4.5.11 Label the self-sealing poly bag, containing sample for in process checks with white “Sample For Analysis” label. 

4.5.12 Perform in process checks in IPQA department and store part quantity of sample for QC analysis in S. S. container with status label.

4.5.13 At the end of the process production person gives product intimation slip.

4.5.14 The IPQA person Checks that the BMR is completed till the current stage and also check the correctness of labelling on the plastic container with respect to product intimation slip.

4.5.15 IPQA person prepares composite sample from the left over samples collected during in process checks, and collect the quantity of sample as per Annexure III in double polybags and affix.

4.5.16 Label (Sample For Analysis) indicating Product Name, Batch No., Batch Size, Manufacturing Date, Expiry Date, Sampled by, Sampled quantity, Sampling Date is kept on the outer surface of the inner self sealing poly bag containing sample for analysis in QC laboratory. 

4.5.17 Record the details of sample collected in the sampling detail register as per Annexure-IV.

4.5.18 Send the composite sample to QC in sample kit with the product intimation slip and sampling details register for acknowledgement of sample receipt and subsequent analysis. IPQA person affixes yellow colour “UNDER TEST” label (as per SOP No. SOP/TAB/046) on all intermediate process / HDPE containers from which the samples were collected.

4.5.19 After receiving the analysis report from QC laboratory and getting it verified by QA, the IPQA person Checks that the analysis of the product passes. After conformation, IPQA person affix green colour “APPROVED” label (as per SOP No. SOP/TAB/046) on all intermediate process containers or HDPE container.

4.6 Sampling of Coated Tablets: 

4.6.1 After completion of coating per lot production person intimate to IPQA person verbally to collect the sample.

4.6.2 IPQA person shall check the following before withdrawing samples from the batch.

4.6.3 Collect polybags, hand gloves etc.

4.6.4 During the manufacturing process the IPQA person goes to processing area.

4.6.5 Wear hand gloves and secondary gown as per the procedure.

4.6.6 Check that the respective stage (Lot) of the process is over and BMR is filled up to the current stage.

4.6.7 Check correct labelling with required product details and stage of operation on the coating pan or details on the container (Product name, B.No., stage).

4.6.8 Collect the samples for in process checks in slightly more quantity for each particular lot from container or coating pan.

4.6.9 IPQA person will perform the in process quality checks as per the BMR and store part quantity of sample collected for analysis in IPQA as per specification and keep the sample in SS container with the status label accordingly.

4.6.10 IPQA person will place the yellow colour “UNDER TEST” label on all the HDPE container of that lot.

4.6.11 If the sampling is to be carried out from more than one HDPE container sampling shall be performed from all number of HDPE container.

4.6.12 Sample can be withdrawn from coating pan for analysis in IPQA as per specification.

4.6.13 Similarly perform the in process checks for all the other lots and keep collecting samples for IPQA analysis in SS container.

4.6.14 Production personnel shall hand over the Product intimation slip to IPQA person after completion of coating stage.

4.6.15 IPQA person will make composite sample from all the lots.

4.6.16 Write product name, B.No., Manufacturing date, expiry date, sign & date on polybag of composite sample in double self sealing polybags. Affix white sample for analysis label on outer side of inner self sealing polybags with batch details.

4.6.17 IPQA person will record the details of samples in the sampling detail register (Annexure-IV)

4.6.18 IPQA person performs the analysis as per specification and enters the values in controlled worksheet copy.

4.6.19 After verifying the report by second IPQA person, the IPQA person affix green colour “APPROVED” label  on all the containers and given release for next stage.

4.6.20 Destroy the remaining quantity of coated tablets and enter the details in sample destruction log book as per Annexure – V.

4.7 Sampling of Finished Products:

4.7.1 During the packing process the IPQA person enter the packing area.

4.7.2 Check that the packing of the relevant batch of the product is ongoing and BPR is filled up to the current stage.

4.7.3 Check correct labelling with respect product details and stage of operation on the status board. (Product Name, B. No., Mfg. Date, Exp. Date, Stage etc).

4.7.4 IPQA person will collect the representative sample of finished product for chemical and microbiological test from the packaging line as per quantity mention in Annexure – III.

4.7.5 Production personnel shall hand over the Product intimation slip to IPQA person after completion of packing stage.

4.7.6 IPQA person will record the details of samples collected in the sampling detail register (Annexure-IV).

4.7.7 IPQA person will send the above samples for chemical analysis and microbiological testing along with the product intimation slip and sampling detail register to QC for acknowledgement of sample receipt and subsequent analysis.

NOTE: In annexure I of this SOP for Product Intimation slip at the place of stage choose appropriate stage from below mentioned different stages but not limited to this:.

1. Intermediate 2. Finished 3. Validation Sample a). Dry Mixing, 

b). Drying, C). Premixing, d). Prepublication e). Lubricated Granules for Dissolution.  f) Optimization, g). Qualification,  h) Exhibit, i) compressed tablet j) coated Tablet k) Capsule etc.

5.0 ANNEXURE

Annexure-1 : Product Intimation Slip

Annexure-2 : QC Sample Label

Annexure-3 : Sampling Quantity At Various Stages

Annexure-4 : Sampling Detail Register

Annexure-5 : Sample Destruction Record

Annexure-6 : Sample for analysis label

Annexure-I PRODUCT INTIMATION SLIP

Product Intimation Slip

To,

IPQA.

Please arrange to collect the following samples. 

Product : 

Batch No. : 

Batch Size :

Pack Code:

Lot No.      : 

Mfg. Date  :    

Expiry Date: 

Stage :

Sample Quantity:

Initiated By  (Production)                                                                             

Received By (IPQA)

Put ‘NA’ wherever not applicable.

Annexure-II QC TEST SAMPLE

 SAMPLE FOR ANALYSIS 

Department: Quality Assurance

Product: 

Batch No.:

EPO No.(if any)

Batch Size:  

Pack Code:

Mfg. Date:    

Expiry Date :           

Stage: 

Sampling Qty.:

Sampled By :    

Date: 

Annexure-III SAMPLING QUANTITY AT VARIOUS STAGES 

Sr.no.	Stages	Quantity
1.	Granules	3 X 5 g (For IPQA)
	Blend	3 X 110g (For Capsules at Q.C.)
2.	Core Tablets	3 X 50 units composite sample for Q.C. analysis
		(a) During friability for IP, BP and USP products follow this standard:   =(3X 80Tablets) + [ 3 X (6.5mgTabletsX1000) ]                                            Avg. wt of tablet In case for tablets with a unit mass of more than 650 mg   = ( 3X 80 Tablets) + ( 3X 10 Tablets)     = No. Of units to be sampled for IPQA Analysis.
3.	Coated Tablets	3 X 30 units composite sample for IPQA analysis
4.	Capsules	3 X 75 units composite samples for Q.C. Analysis.
5.	Finished goods	(a) During friability for IP, BP and USP products follow this standard:   =(3X 80Tablets) + [ 3 X (6.5mgTabletsX1000) ]                                            Avg. wt of tablet In case for tablets with a unit mass of more than 650 mg. = (3 X 80 Tablets) + (3 X 10 Tablets)   = No. Of tablets units (round up to pack style) to be sampled for Q.C. Analysis.
		2X1000 capsules composite sample for Q.C. Analysis.
		(3 x 10 g / average weight of tablet or capsules) = No. Of Units to be sampled for microbiological testing
6.	Granules/Blend/Core/Coated/ Finished (in case of Validation batches)	As per Protocol

  Annexure-IV SAMPLING DETAIL REGISTER

Sr. No.  

Date 

Product

Name

B.No.

B.Size

Mfg.Date

Exp.Date

Stage

Intimation Slip No.

A.R.No.

Sent By

Received By

Report received by IPQA

Release Status with Date

Annexure-V SAMPLE DESTRUCTION RECORD

Sr. No.

Product Name 

B.No.

Sample Quantity

Sample Quantity used for analysis

Sample Quantity Destroyed

Destroyed On

Destroyed By

Annexure-VI SAMPLE FOR ANALYSIS 

Department: Quality Assurance

Batch No.  :          

Sampling Qty.:

Sampled By :