Sop for sampling of sterile API 

This Document describes (Standard Operating procedure) Sop for sampling of sterile API.

Sop for sampling of sterile API

I. Purpose & Scope:

  • The purpose of this SOP is to lay down the procedure for sampling of Sterile API

II. Responsibilities:

  • All Quality control personnel’s shall be responsible to follow and implement this SOP i.e. sampling of sterile API.

III. Introduction and Procedure :

Precautions taken during sampling of sterile API :

  • All sampling of Sterile API activity must be performed under RLAF.
  • In case of power failure during sampling activity close the Material Containers as early as possible. Restart the sampling of sterile API activity after 15 minutes of starting of RLAF and sanitization of area and record the observations in the log book.
  • After sampling of each consignment, sampling person and workmen shall disinfect the hands with 70 % IPA solution kept in the Sampling Room.
  • In case, if two different raw materials to be sampled on same day. Perform the sampling of sterile API of one material at a time, then all sampling person should come out in exit air lock and performing the de-gowning procedure and enter into Air lock I. Then re-enter the Airlock II and performing the gowning procedure and then enter sampling room for sampling of next material.
  • In case, if two or more batches of same raw material to be sampled on same day, perform sampling one by one by following cleaning after each batch.
  • Use sterilized/depyrogenated sampling device of appropriate size for individual batch only, after use put it in appropriately labeled polybag. All sampling devices shall be transferred to Unit preparation area for cleaning at the end of the activity.
  • Before sampling of Sterile API, ensure that calibration/verification of Analytical balance is performed.

Preparation of Sampling Accessories during sampling of sterile API :

  • For sampling of Sterile API, follow the washing, drying, sterilization procedure for sampling accessories as per respective SOP.
  • Sampling for Microbiological and chemical testing shall be done in separate sterile polybag/ bottle.
  • Sampling bottles: For BET testing use depyrogenated bottle or vial. For Sterility testing and Chemical testing use sterile bottles/polybags.
  • SS Spatula: Perform the washing and drying of SS Spatula, then wrap it in 3 layer of Aluminum foils and Depyrogenate/Sterilize in validated cycle.
  • All the sampling accessories shall be kept in SS Sampling Kit and transfer them to stores area along with sampling labels (Under test labels, Sample labels) and Checklists.

Sampling Methodology for sampling of sterile API :

  • At receipt of the raw material; Goods Receipt Note (GRN) shall be prepared by warehouse and it shall be handover to QC for planning of sampling & analysis.
  • GRN shall be accompanied with COA of the Manufacturer.
  • Enter the GRN details in to ‘Raw material (Sterile API) Inward register’. Refer Annexure I.
  • QC department shall generate the A.R No. in a sequential manner.
  • Prepare the sampling kit as per sampling plan and requirement. Refer Annexure II (List of items to be carried for sampling) for fulfillment of sampling accessories before leave for sampling.
  • Verify the details of consignment against GRN and same is recorded on ‘Sampling checklist for sterile API’. Refer Annexure – III.
  • During verification, if any discrepancy is observed like seal of container is not proper or container is damaged/dirty, label of container is not readable or any other discrepancy observed; immediately report to Warehouse person, Head QC and Head QA for necessary action.
  • After successful verification, transfer the sampling kit and accessories to sampling room through Dynamic Pass box.
  • Before transfer the material, clean and sanitize outer surface of containers, sampling kit with 70% IPA and kept it under UV light of Dynamic Pass box for 5 to 10 minutes.
  • Follow the Entry procedure  and enter into sampling area.
  • Check and verify for cleanliness of sampling room as per the checklist mentioned in Annexure V. If area found unclean, get it cleaned before sampling. Name of the previous sampled material should be taken from the Sampling log book.
  • Switch ON the RLAF unit at least 15 minutes prior to sampling and record the pressure of RLAF after 15 minutes in the sampling log book as per Annexure IV.
  • Switch ON the balance and wait for 15 to 30 minutes to stabilize the balance. Production person shall perform the calibration / verification of balance.
  • Label the sampling containers (bottles/polybags) appropriately with the concerned test name.
  • Carry out the whole sampling procedure under RLAF.
  • Maintain the aseptic conditions throughout the sampling procedure.
  • Carry out sampling from all the containers i.e.100% sampling shall be performed.
  • Containers shall be taken through the pass box after exposure of UV for about 5 minutes, keep them into sampling area.
  • Open a single container at a time in RLAF and withdraw the approximate quantity of sample by using sampling device of appropriate size. Quantity taken shall be considered on the basis of individual sampling quantity required. Close the container and kept it aside.
  • Take next container and perform the sampling as above. Follow the same procedure for remaining containers.
  • Separate samples shall be withdrawn for Sterility test, BET test and Chemical analysis.
  • For Identification Test, collect sample from each container, in individual polybags.
  • For sampling quantity details, refer specification of that specified product.
  • Mention the sampled quantity on GRN which should specify the detail quantity sampled for Identification test, Chemical analysis, Microbiological analysis and Controlled sample.
  • Generally for Chemical analysis and Control sample 30 gram sample shall be withdrawn, For Sterility and BET testing 10 gram sample (8 grams for sterility and 2 grams for BET Purpose) shall be withdrawn.
  • For Identification Test approximate 100 mg sample shall be withdrawn from each container in individual polybag.
  • Sampling quantity from individual container shall be decided by considering the total sampling quantity and total numbers of containers to be sampled.
  • For example : If consignment is of 10 containers of Cefuroxime sodium sterile is to be sampled, then for Microbiological analysis (Sterility and BET) withdraw 1 gram of sample from each container in one depyrogenated bottle to make total 10 grams sample. For complete chemical analysis (chemical and control sample) withdraw 3 grams from each container to make 30 grams composite sample.
  • Close the lid of each container after sampling and seal with UV exposed tape and further sanitize with 70% IPA.
  • Use different sampling devices for different materials. In case any discrepancies found in sampling device, shall be replaced.
  • Follow the specific instructions as indicated on containers (if any) for storage.
  • Label the containers/packs which are selected for sampling as N/1/n, N/2/n….. N/S/n (‘N’ stands for total number of packs/containers, ‘S’ for serial number of container selected for sampling and ‘n’  for total number of containers taken for sampling.) Then affix the “Under Test” labels.
  • After sampling, collect all samples and sampling accessories in sampling kit. Keep the Sampling kit in Pass box  and exit from the area as per SOP.
  • After exit from sampling area, take sampling kit from Pass box  and transfer it to Quality Control laboratory.
  • Mention the sample quantity for Chemical test, Microbiological test and Control sample in Annexure –VI.
  • Distribute the chemical sample into ‘Sample for chemical analysis’ and ‘Control sample.’ Give it to respective analyst. Microbiological sample shall be given to Microbiologist.

Cleaning of Sampling Area after sampling of sterile API :

  • Area shall be cleaned between each sampling activity.
  • Clean the balance and plugs, wires, Pass box with dry lint free cloth.
  • Clean the inner and outer surface of RLAF
  • Clean the floors, walls, doors and Glasses
  • Clean the area with dry lint free cloth followed by mopping with disinfectant solution.
  • Update the area status of Sampling Room as “Cleaned”.
  • Record the cleaning activity in Annexure IV.


IV: Annexure:

Annexure I :  Raw material (Sterile API) inward register.

Annexure II  :  Sampling Kit (List of items to be carried for sampling)

Annexure III    : Sampling check list for sterile API

Annexure IV    : Sterile API Sampling Log Book

Annexure V    :  Sterile API Sampling area Cleaning Check List.

Annexure VI   :  Sterile API Sampling Receiving Register




Raw material (Sterile API) inward register.


Sr. No. Date of Receipt GRN NO. Name of Raw Material Vendor B. No. Mfg.Date Exp.Date Received Qty. Mfg. By Suppliers Name A.R. NO. Sampled by/ Date Remark


           Annexure -II

Sampling Kit (List of items to be carried for sampling)


Sr. No. Items
1 Appropriate no. of “under test” labels.
2 “Sampled” labels.
3 “Sample for Analysis” label.
4 “Control sample” label.
5 Appropriate no. of Sterile poly bags.
6 Appropriate no. of Sterilized glass bottles /Depyrogenated bottle/ Sterilized Spatulla / Depyrogenated Spatulla.
7 Scissors/ cutters
 8. BOPP Tape
9 Seals




Sampling check list for sterile API

ITEM NAME : ____________________________              A.R.NO.:_____________

BATCH NO.  : ____________________________              DATE    : _____________

(A) For Goods Receipt Note
1 G.R.N. No. Present / Not Present
2 Item Code Present / Not Present
3 Item Name Present / Not Present
4 Name of Manufacturer & Supplier Present / Not Present
5 Source of Material Approved / Not Approved
6 Batch No. Present / Not Present
7 Manufacturing Date Present / Not Present
8 Expiry Date Present / Not Present
9 No. of Packages / Containers Present / Not Present
10 Party’s / Manufacturer COA Present / Not Present
(B) For Consignment
1 Location As Per Standard AC/ NON AC
2 Standard Packing ———
3 No. of Packages / Containers ———
4 Batch No. Present / Not Present
5 Manufacturing Date Present / Not Present
6 Expiry Date Present / Not Present
7 Observation for Material (if any):
(C) Description of Sample Quantity: a)    Identification Test:

b)    Chemical Test:

c)    Microbiology Test:

d)    Control Sample:

(D) Total withdrawn Sample Quantity:


Remarks: ________________________________________________________

Sampled By:                                                               Reviewed By :

Date            :                                                               Date               :




Sterile API Sampling Log Book

Date Differential Pressure  

RLAF Started at



Materials Name & Grade




B.  No./  Lot No. A. R. No.  


Temp. in Sampling Room           ( NMT 25 C)



RH in Sampling Room                  (NMT 55 %)

No. of containers in consignments Container for sampling Sampling Time Sampled By Sampling area Cleaning Time Sampling area cleaned by Area cleaning checked by
Sampling room


(0.6 to 1.5mm of water)

Magnehelic gauge HEPA filter

(8mm to 20mm)

From To From To











Annexure – V

           Sterile API sampling area cleaning checklist 











Particulars Cleaning status
1) Surrounding area of sampling room


Satisfactory /Not satisfactory
2) Over gowning room


Satisfactory /Not satisfactory
3) Sampling device


Satisfactory /Not satisfactory
4) Floor in sampling room


Satisfactory /Not satisfactory
5) Bench kept under RLAF


Satisfactory /Not satisfactory


Satisfactory /Not satisfactory
7) Balance


Satisfactory /Not satisfactory


Remarks (if any):





Verified By (Sign. / Date):








Annexure – VI

Sterile API Sampling Receiving Register


Date Name  of Material Batch No. A. R. No. Sample for Chemical analysis with Identification Test Sample for Microbiology analysis Control Sample
Qty. Received By (Sign. / Date) Qty. Received By (Sign. / Date) Qty. Received By (Sign. / Date)



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