PURPOSE : To provide the Procedure to be followed for sampling of all raw materials.
SCOPE : Applicable to all raw materials received in LL units.
RESPONSIBILITY: Analyst, section head, Head Quality Control, Production officer
DEFINITION :
Sampling: Sampling is the process of abstraction of a representative portion of material or a group of units from a larger quantity of material or collection of units. Sampling is done in order to test a small portion and obtain information that can be used as a basis for action on the large quantity or collection of units or for monitoring the production process. Since the logic of sampling is that of generalizing with the information obtained from a portion about the whole batch /consignment, a sample must accurately represent the batch / consignment that is being tested.
Sample: A sample consist of a small quantity/unit(s) one or more units of material/ product drawn from a lot or a batch, quantity of sample being collected at random without regards to their quality. The number of units or quantity of material, product in the sample is the sample size.
QC Sample Pack: It is a representative sample quantity received along with the consignment from the manufacturer which can be used as “sample for analysis” provided proper validation is available.
Raw Material: Any ingredient intended for use in the production of APIs. These may include starting materials, process aids, solvents, and reagents.
Active Pharmaceutical Ingredient (API): Any substance, which is therapeutically potent with pharmacological activity intended for use in the manufacture of a drug product.
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PREPARED BY REVIEWED BY APPROVED BY User Department Department Head Unit Quality Assurance Date: Date : Date: |
1.0 HEALTH, SAFETY AND ENVIRONMENT:
During sampling of propellants, avoid contact with skin, inhalation, and eye During sampling wear cold resistant gloves. Propellants are not flammable.
2.0 PROCEDURE:
2.1 Before sampling ensure that:
2.1.1 The specification of concerned material is referred for the characteristic of the material e.g. light sensitive, temperature sensitive etc., category of material like hormones, cytotoxic, steroids etc, storage conditions, pack description, necessary safety precautions and personal protective equipment to be used.
2.1.2 The basic labeling requirements are met pertaining to material details. Also the required information to distinguish specific characteristic from different similar types should be indicated e.g. viscosity in case of material of different viscosities like 3 cps, cps etc., type of polymorph in case of different polymorphic groups etc.
- The consignment has a yellow rope or is stored in quarantine area.
2.1.4 The manufacturers / suppliers status label(s) (approved label) is defaced with “cross” marks, sign and date by store person.
- The containers are clean.
- The containers are stored properly on pallets/racks.
- It should be adequately segregated from other lots or batches.
- The material is not exposed, in the case of damaged containers / packs. (If any)
2.1.9 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 immediately; perform sampling only after corrective action has been taken. Switch ‘ON’ the LAF / RLAF / UDAF for at least 30 minutes, prior to commencement of sampling activity. Record the details. Refer
For microbiological analysis sampling should be done separately using sterile
equipments / accessories as given in the individual specification. For sampling
of the materials for the Bacterial Endotoxin Test, depyrogenated accessories
and de-pyrogenated vials or bottles should be used. Following precautions
should be taken by the chemist while sampling for Microbiological Testing.
- Sampling of raw material / sterile packaging material should be performed
under LAF / RLAF / UDAF.
- Check the integrity of the sampling accessories / equipments visually and
the ‘Use before date’ before sampling.
- While sampling wear snood / gown, sterile powder free hand gloves, shoe covers/ booties.
- Disinfect the gloved hands with the hand disinfectant solution.
- Remove the wrapper of sampling accessories such as spatula / spoon or open bottle / polythene bag.
- Carry out the entire sampling activity (for raw materials) i.e. balance position, operator position at 90° to the air flow pattern.
- After sampling close the sterile polythene bag/bottle taking proper
- For sampling activities carried out in the manufacturing area, follow the proper precautions for the transfer of the accessories into the area. The
sampling accessories or activity should not impact on manufacturing process and products.
2.1.13 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 as per the specification.
2.1.14 While sampling, ensure that both the requirements should be complied i.e. Total quantity of sample (Required for Individual identification test,
complete analysis and reserve samples) as well as the minimum withdrawal of sample from individual container, specified in the respective specification.
e.g. As per specification total sample quantity required is 30 g and minimum quantity to be withdrawn per container is 5 g.
2.1.15 Consider the following cases:
Case 1: If the total number of container to be sampled is equal to 10. Then to fulfill the requirement of total quantity required and the minimum quantity to be sampled per container, 5 g of the sample is to be withdrawn from the individual container which becomes 10 x 5 g = 50 g total sampled quantity.
Case 2: If the total number of container to be sampled is equal to 5. Then to fulfill the requirement of total quantity required and the
minimum quantity to be sampled per container, 6 g of the sample is to be withdrawn from the individual container which becomes 5
x 6 g = 30 g total sampled quantity.
2.1.16 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.
2.1.17 For solids, withdraw portions from different parts of “the bulk in the container in order to get a representative sample, and collect it in a polythene
bag. Similarly repeat for different containers. For liquids, mix the contents of the container by gentle swirling, using a liquid sampler / sampling pipette,
withdraw the amount specified in the individual Specification into labeled bottles.
2.1.18 For chemical analysis sample should be drawn as mentioned in the specification into individual polythene bags / Bottles / Container of suitable size as mentioned in the respective specification (as per the number of containers to be sampled).
2.1.19 For microbiological analysis sample should be withdrawn into a sterile polythene bags / bottles /vials as mentioned in the respective specification as follows
2.1.20 Withdraw the sample from the individual container into the sterile polythene bags / bottles / vials using the suitable sterile sampling equipment. Check for color and extraneous matter.
2.1.21 Withdraw the sample from the second container to the same sterile polythene bags/ bottles or container containing the content of first container and seal the same properly.
2.1.22 Hold the polythene bag from both the sides and shake horizontally (left to right and vice versa) in order to get homogeneous sample. In case of liquid sample, swirl the bottles to get the homogeneous sample.
2.1.23 Withdraw the sample from the third container to the same sterile polythene bags /bottles or vials containing the content of first and second container and seal the same properly. Hold the polythene bag from both the sides and shake horizontally (left to right and vice versa) in order to get homogeneous sample. In case of liquid sample , swirl the bottle to get the homogeneous sample.
2.1.24 Follow similar procedure for the remaining containers to be sampled, Collect the sampled quantity in the same sterile polythene bag / bottle and mix / swirl the sampled material properly to get an homogeneous sample.
2.1.25 Withdraw the sample quantity required for reserve sample for microbiology and utilize the remaining quantity for microbiological analysis.
2.1.26 Protect the sample and the material being sampled from external contamination at all stages of sampling. Check for any lumps/black particles/extraneous matter, and if noticed, indicate in the remarks column of the sampling checklist. Transfer the polythene bag containing the sample into another polythene bag.
- Check the description of the sampled material against the standard description specified in the specification. If material does not comply with the specification, inform immediately to the QC Head and after consulting with cipla representative take, the corrective action to reject the consignment.
- For sensitive materials like hygroscopic, light sensitive etc. sampling to be done in suitable area in order to avoid exposure.
2.1.29 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.
- SAMPLING OF RAW MATERIALS
Note: Sampling should be carried out in designated area in Stores.
2.2.1 Consignment received directly from the supplier/ Manufacturer Remove from ‘To be sampled’ file, GRN of items, which are to be sampled.
- Check the details on the GRN for all the details relevant for sampling and note the observations on the sampling checklist for sampling of Raw Materials refer Annexure LLQCD-03/A1.
2.2.3 Read the Sampling and Handling section of the Specifications for the material in order to know the quantity and manner in which sampling should be carried out.
2.2.4 From the information obtained arrange for the requisite number of sample bags / bottles, labels, the right sampling accessories and where applicable, the protective gear and any other safety accessories. For hazardous / corrosive materials, arrange for a suitable carrier for transporting the samples.
Prepare requisite numbers of ‘Under Test’ labels. Labels are to be prepared equivalent to the total number of containers to be sampled and one additional label bearing container No. (“0 / -“) for the ‘Consignment Details’ card.
2.2.6 Enter all the details on the ‘Sample for Analysis’ labels, refer Annexure LLQCD-03/A2 and affix them to the polythene bag/sample bottle. Alternatively printed ‘Sample for Analysis’ labels may be used.
2.2.7 Check the details from the sampling intimation document i.e. G.R.N. against the respective challan and make the related entries in the sampling checklist. Refer Annexure LLQCD-03/A1.
2.2.8 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
| UNIT NAME
VERIFIED BY “QC” Sign: _________ Date: __________
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2.2.9 If the material received is not as per intended grade, the same is to be informed to the concerned manufacturer through warehouse for the required action, required follow up should be done to obtain the required grade material. Wherever the manufacturer is not ready to provide the same (e.g. IP grade material not provided by import or overseas vendors), the comments regarding the same should be recorded in the sampling checklist. Sampling to be performed and compliance of the material to the required grade to be checked by testing.
2.2.10 If the COA received is not as per the current pharmacopoeia, the same is to be intimated to the concerned manufacturer through warehouse for the required action, required follow up should be done to obtain the COA as per current Pharmacopoeial requirement. Wherever the manufacturer is not ready to provide the same, the comments regarding the same should be recorded in the sampling checklist. Sampling to be performed and compliance of the material to the current pharmacopoeia to be checked by testing.
2.2.11 For the sampling use the sampling kit consisting of the respective Specification, Sampling intimation document, sampling checklist, checklist for cleaning and line clearance of sampling room, properly labeled sample containers (self-sealing polythene bags / bottles), sampling accessories, safety apparels etc.
2.2.12 Locate the consignment in the store department by referring to the information from the GRN and ‘Location Board / Chart’. Material to be sampled should be available in the quarantine area or covered with a yellow rope / chain.
- Check the entries on the ‘Consignment Details’ card against the information given on the GRN.
2.2.14 Check the manufacturer’s label affixed on the consignment against the entries given on the GRN. Enter the details of this checking in the sampling checklist. Refer Annexure LLQCD-03/A1.
2.2.15 Review of consignments as specified above should be done even if a separate “QC Sample pack” is received and to be documented in sampling checklist. If the quantity of the QC Sample pack is considered in the GRN, this quantity should be considered while including the sampled quantity in IMS. If the quantity of the QC Sample pack is not considered in the GRN, this quantity should not be considered while including the sample quantity in IMS.
- In case of material stored at specific condition e.g. at 2 – 8° C / or in a deep freezer, allow the material to attain the room temperature before doing the
sampling.
Before sampling, review the sampling area for usage record, line clearance and cleaning status to ensure that the area is suitable for sampling. Also check the calibration status of the balance. Refer Annexure LLQA –
13/A3 and Annexure LLQCD-03/A4.
- Ensure that during the entire sampling activity the sampling accessories (when not in use) are kept inside polythene bag under LAF/RLAF /UDAF.
- In case of API all the containers are to be sampled.
2.2.20 In case of inactive materials, if the consignment is of three or less than three containers then all containers are to be sampled. If the number of containers are more than three and are up to the 100, then sampling to be done as per (√n + 1), where n = total number of containers. If consignment is of more than 100 containers, sample one additional container for every 100 container and thereafter. If the calculated value by (√n + 1is fractional, then it should be rounded off to the higher side, e.g. If total number of containers are 10, then square root of the same is 3.16; in this case, (√n + 1 is to be considered as 3.16+1 = 4.16 i.e. = 5.
2.2.21 In case of the excipient to be used for the parenteral dosage form/ for Inhalers, all the containers are to be sampled.
2.2.22 In case of solvents stored in tanks, the circulation pump should be started for about 30 minutes. After 30 minutes, appropriate quantity should be drained in a bucket and then the required quantity of sample should be collected in individual clean and dried glass bottles bearing ‘Sample for Analysis’ label.
- Take one lot/ batch for sampling at a time. Open one container at a time and collect the sample from the container in a self sealing polythene bag ensuring that the amount mentioned in the Specification is drawn by weighing on the sampling balance for solids and for liquid collect the sample in a bottle ensuring that the amount mentioned in the specification is drawn by using appropriate sampling equipment. Avoid spillage during sampling. In case of spillage, appropriate procedure to be followed based on material characteristic.
- After completion of the sampling immediately, reseal the individual container of the consignment properly e.g. incase if the material is packed in the polythene bag, reseal the individual polythene bag using the fastener and for liquids, stopper the bottle immediately. In case of the drum, close the lid of the same properly.
- After sampling, affix the duly signed ‘Under Test’ labels just below the manufacturer’s label on the containers or incase of insufficient space at the
side of the manufacturer’s label from which the sample is withdrawn.
For containers where sticker labels cannot be affixed, stick the labels on
cardboards and tie them to the containers.
2.2.26 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.
2.2.27 In case of gas cylinders, sample all cylinders and collect into separate dedicated Rubber bladders / Tedlar bags / Aluminium containers. Collect samples after flushing repeatedly for 2 to 3 times.
2.2.28 In case of sensitive materials (e.g. thermal labile, highly oxidative etc), sterile materials or costly materials, separate “QC Sample pack” should be demanded from manufacturer along with consignment and sampling from consignment should be avoided.
2.2.29 In case of sensitive materials having microbiological test requirement , preferably a separate “QC Sample pack for microbiological analysis should be demanded mentioning the quantity of sample required for analysis from the manufacturer. If separate “QC Sample pack” for microbiological analysis is not received, withdraw quantity for microbiological analysis by microbiologist from sample pack initially and then only proceed for chemical analysis.
2.2.30 Validation of vendor for minimum three consignments for “QC Sample pack” to be performed for appropriate sampling procedure (to provide representative samples of entire batch), proper packing and sealing, sufficient quantity, proper labeling (with adequate information about consignment traceability), quality of material received in “QC Sample pack” against the sample of consignment etc.
2.2.31 Wherever QC Sample pack is received from manufacturer along with consignment, it is to be treated as sample for analysis.
2.2.32 Enter the details of sampling such as Quantity sampled (e.g. 5 x 10 g which indicates 10 g sample is withdrawn from each of 5 containers), date of sampling and signature of the sampling analyst on the GRN and sign the sampling checklist. In case if sample for microbiological analysis is withdrawn, indicate the quantity withdrawn for chemical analysis and microbiological analysis separately (e.g. Chemical: 5 x 10 g, Microbiological: 5 x 2 g). In case if “QC Sample pack” is received, enter the details of quantity received on the GRN.
2.2.33 On completion of sampling, keep the sampled container in designated area and affix the duly signed ‘Under. test’“0 / -“ number label on consignment card.
2.2.34 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 back in the sampling kit / polythene bags to the Quality Control washing area.
2.2.35 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 LLQCD-03/A3 and Annexure LLQCD-03/A4.
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 properly until taken for analysis e.g. for material stored at 2 – 8 ° C / Deepfreeze condition, store the sampled material in respective condition. Incase of microbiological samples arrange to sent for testing promptly. Keep the sampling intimation document in the ‘To be analysed’ file.
Arrange for the cleaning of the sampling accessories and the proper storage of the sampling and safety accessories with status label. ‘Cleaned’.
2.2.37 For items (solvents) received in tankers, perform the sampling as follows:
2.2.37.1 Ensure that the tanker is parked in designated place and proper earthing is done. Check the seals at all the points i.e. upper lid and bottom valve of the tanker, it must be intact. Before commencement of sampling ensure that all points are cleaned.
2.2.37.2 Drain 3 to 4 liters of solvent from bottom of the individual compartment in a bucket and do the visual inspection. Also collect the sample from all compartments of tanker from top using glass-sampling tube to individual 125 ml glass bottles and do visual inspection.
2.2.37.3 Collect samples from individual compartments separately into labeled bottles indicating the compartment number. From each compartment, withdraw the sample from top and bottom into the same bottle.
2.2.37.4 If visual inspection fails, inform the Section Head and Store officer for further action.
2.2.37.5 If the visual inspection passes, then use the sample collected in individual bottles during visual inspection for further testing.
2.2.37.6 Inspect all samples for homogeneity, clarity and extraneous matter. Report the observation in sampling checklist in remark column.
2.2.38 For the sampling of Propellants [received in Tanker/Tonner (Tank with
1000 Kg capacity, follow the procedure specified below]:
2.2.38.1 Identify the consignment, check the GRN against the consignment card and ensure that the details are tallying.
2.2.38.2 Keep the sampling kit on a polythene bag in front of the Tanker / Tonner /BST which is to be sampled.
2.2.38.3 Tare the sampling cylinder weight on the weighing balance. Break the seal, unscrew the cap/ flanze of the outlet valve of the Tanker/ Tonner / BST and keep it on the polythene bag.
2.2.38.4 Clean the inner side of the outlet valve with Lint free duster and Acetone.
2.2.38.5 Attach suitable connecter, flexible tube, sampling cylinder horizontally to the Tanker/ Tonner/ BST.
2.2.38.6 Slowly open the valve using adjustable spanner and flush the tubing with little amount of propellant. Collect the sample in a duel valve sampling cylinder; close the valve of Tanker/ Tonner/BST and Inlet valve of sampling cylinder.
2.2.38.7 Unscrew the tubing slowly, let the material retained in the tubing to come out and evaporate. Reattach the cap of the outlet valve of Tanker / Tonner/ BST.
2.2.38.8 Check the sample quantity on weighing balance. Keep back all the sampling accessories and the sample in the sampling kit. Affix the ‘Under Test’ label to the consignment card and to the outlet valve/ sampling point.
2.2.39 For the sampling of Vitamins (Which are received as ampoule e.g. Vitamin D3):
2.2.39.1 For Vitamins, separate “QC sample pack” should be demanded from manufacturer along with consignment. In case, “QC sample pack” is not received follow the following procedure:
2.2.39.1.1 Do not sample from ampoule of the consignment; collect one ampoule as a sample for analysis. Keep one intact ampoule as reserve sample (store between 2°C and 8°C).
2.2.39.1.2 While sampling, break the seal of ampoule gently and remove the sample into individual non-toxic, self sealing black polythene bag or amber colored clean and dry glass vial. Protect the sample from light and air by purging under nitrogen.
2.2.39.2 Plan the sampling just prior to the analysis. After sampling, immediately analyse the sample as per specification, as the material is sensitive to air, heat and light.
2.2.39.3 Before dispensing, Stores should intimate to Quality control by raising the intimation from stores mentioning number of containers required for dispensing.
2.2.39.4 Container/ pack should be tested for individual identification by withdrawing the sample at the time of dispensing as per intimation from Stores.
2.3 Sampling for Reanalysis
2.3.1 Check the details on the reanalysis GRN and make the entries in the checklist for sampling of Raw material. Refer Annexure LLQCD-03/A1.
2.3.2 In case the re-analysis GRN, withdraw the sample quantity required for re-analysis testing.
- Deface the ‘Quarantined for Reanalysis’ labels pasted on the Passed label of each container with sign and date.
- Follow procedure for sampling as given under ‘Consignment received directly from supplier / manufacturer’.
2.3.5 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 reanalysis material is in the quarantine area or with
Yellow rope.
2.4 Sampling of consignments received on Stock Transfer Memo (STM)
2.4.1 Check the details on the sampling intimation documents GRN and make the entries in the sampling checklist. Refer annexure LLQCD-03/A1
2.4.2 Follow procedure for sampling as given under ‘Consignment received directly from supplier / manufacturer.’
2.4.3 Withdraw the sample quantity required for STM 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.
2.4.4 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
3.0 ABBREVIATIONS:
| GRN | : | Goods Received Note |
| API | : | Active Pharmaceutical ingredient |
| LAF | : | Laminar Air flow |
| RLAF | : | Reverse Laminar Air flow |
| UDAF | : | Uni-directional Air flow |
| BST | : | Bulk Storage Tank |
| COA
IMS TSE |
:
: : |
Certificate of Analysis
Inventory management system Transmissible spongiform encephalopathy |
REFERNCES:
QCP-06 : Sampling
5.0 ANNEXURES:
| Annexure LLQCD-03/A1 | : | Checklist for sampling of raw materials |
| Annexure LLQCD-03/A2 | : | Label for sample for analysis |
| Annexure LLQCD-03/A3 | : | Area cleaning and usage record of sampling room |
| Annexure LLQCD-03/A4 | : | Checklist for cleaning and line clearance of sampling room |
| Annexure LLQCD-03/A5 | : | SAMPLED Stamp
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| Annexure LLQCD-03/A6 | : | General flow diagram for sampling |
| Annexure LLQCD-03/A7 | : | Entry-exit, usage and cleaning of sampling room(Raw material(API and Excipient) |
