Friday, December 24, 2010

Raw Material (Rm) Sampling, Analysis And Approval (Non-Sterile)

Raw Material (Rm) Sampling, Analysis And Approval (Non-Sterile)

1.0              OBJECTIVE

The objective of this SOP is:
1.1               To describe the procedure for sampling representative material from each lot / Batch Number of Raw Material (RM) in sampling room.
1.2               To describe the procedure for analysis to be carried out for each lot / Batch Number of RM.
1.3               To describe the procedure for review and approval of each lot / Batch Number of RM.

2.0              RESPONSIBILITY

2.1               The Chemist - Quality Control (QC) shall be:

2.1.1.        Responsible for receiving the GRN and entering the details in RM register.
2.1.2.        Responsible for the ensuring appropriate cleaningness of sampling room including LAF unit, sampling devices before sampling.
2.1.3.        Responsible for ensuring proper documentation for sampling and assembling of adequate number of items for sampling.
2.1.4.        Responsible for monitoring of sampling room for environmental conditions and differential pressures.
2.1.5.        Responsible for proper sampling of RM from the container (s) and its appropriate identification on each sampled container (s).
2.1.6.        Proper labeling of containers.

2.2         The Executive – Quality Control shall be:

2.2.1          Responsible for distribution of work for sampling and analysis of material(s) to sub-ordinates as per training imparted.
2.2.2          Responsible for verifying the recorded results by Quality Control – Chemist and review of the results against standard limits.
2.2.3          Responsible for updating the document as per regulatory requirement
2.2.4          Responsible for maintaining the laboratory neat, clean and tidy.
2.2.5          Responsible for ensuring all laboratory instruments are calibrated and working satisfactory.
2.2.6          Responsible for imparting training to sub-ordinates for Good Laboratory Practice (GLP).

2.3         The Departmental Head – Quality Control shall be:

2.3.1          Responsible for overall maintenance of sampling room, laboratory and all analytical instruments.
2.3.2          Responsible for final review of the results and for decision for approval or rejection of RM under consultation with QA.
2.3.3          Responsible for updating pharmacopoeial and regulatory requirement, standard limits and Good Laboratory Practices (GLP) from time to time.


Head – Quality Control

4.0.        PROCEDURE:


4.1.1          Receive 3 computerized copies of Goods Receipt Note (GRN) from Warehouse
4.1.2          Report to Executive – QC for the receipt of the GRN.


4.2.1          Enter the details from GRN in RM Register kept in Quality Control Lab Refer Annexure-1.
4.2.2          Fill up the details of GRN in bulk inspection sheet in E-com system (Refer Annexure- 2).


4.3.1          Refer SOP for detailed entry, exit, gowning and Degowning procedure.
4.3.2          Check and verify the sampling room with regards to cleaning as per Cleaning SOP, Refer as per SOP .
4.3.3          If any of the location mentioned in Cleaning Record is not clean get it cleaned before sampling. 
4.3.4          The differential pressure of all magnehelic gauges in the sampling area corridors shall be recorded in the format given in Annexure – 8
4.3.5          Switch on the reverse Laminar Air Flow (LAF) unit before 15 min. for sampling of RM. Refer Annexure- 3 (Sampling Operational Log Book). Check and record the following:    Room temperature and humidity    Cleaning records    Balance verification record    Reading of Magnehelic gauges reading 


4.4.1          Take the GRN and sampling remark format and go to Warehouse – Raw Material Quarantine area.
4.4.2          Verify the details of GRN as against container(s) like:           Name of the material           Manufacturer’s name           Specification (if any)           Mfg. date / Expiry date           Pharmacopoeial status           Approved Vendor Status           Quarantine Label status.           Certificate of Analysis of Party

4.4.3          Bring the RM container(s) nearer to the sampling room on clean pallet.
4.4.4          Clean the container from outside before taking in sampling room.
4.4.5          Take the material container (s) inside the sampling room one after another and number each container as Container No.­­ of N­­­­­­ where N is the total number of the containers received in the batch / lot.
4.4.6          Open the containers under Reverse Laminar Air flow (RLAF) only one after other.
4.4.7          During sampling do not keep two different material container(s) as well as different batch of same materials at a time to avoid any mix-up.
4.4.8          Use sampling device of appropriate size for one material only, then after use put it in appropriately labeled recycled bin.
1.   In case of sampling more than one batches of same material, use different sampling devices.
2.   Follow the specific instruction as indicated on containers to be sampled   & Sampler’s
      Remark for sampling


4.4.9          Take special precaution while sampling liquid materials like solvents.  Use special S.S. device/Glass tubing only for liquid.

4.5              SAMPLING OF RAW MATERIAL  (Non-Sterile)

4.5.1            Check and record the daily verification of Balance.  Refer Annexure – 4 for procedure and record sheet.
4.5.2            For all active / Inactive (Excipients) materials carry out √N+1 sampling .
4.5.3            Physically damaged container (s) without seal shall be assessed for intactness of innermost packing. Physically damaged container (s) shall be rejected and it shall be reported to Head QA / QC for information.
4.5.4            Before starting sampling, ensure that sampling area is cleared of all previous traces of materials and is in cleaned condition. Record the temperature and humidity in the format mentioned in Annexure – 5.
4.5.5            Ensure that the manometer reading should be 8.0 - 15.0 water column across HEPA filter and negative pressure across the pre filter should be 2.0 to 5.0 mm of water column.
4.5.6            Observe visually for appearance of the material for any abnormalities like discoloration, lumps, non-characteristic odour, foreign matter, physical heterogeneity etc.
4.5.7            In case of any abnormalities observed, inform to Head – QA / QC for final disposition.
4.5.8            Record all observations in Sampler’s Remarks format.
4.5.9            Material of only one batch Number shall be sampled at a time.
4.5.10        Collect the sample from top, middle and bottom and mix it to form a homogeneous sample.
4.5.11        Withdraw approximately equal quantities from all containers / packs for preparing pooled sample (Composite Sample) using following clean sampling equipments.

Thick Glass Tube / S.S. sampling device
For liquid sampling from drums
Glass pipette with Rubber bulb
For liquid sampling from bottles / cans.
Sampling Rod / Spatula
For sampling of material from solid bulk containers.

4.5.12        Label the amber coloured glass bottle in which samples are taken with appropriate pooled Sample (Sample for Analysis) label refer Annexure - 7.
4.5.13        Simultaneously withdraw quantities as mentioned in sample Quantity list for analysis for the composite sample. Sample the quantity sufficient for 2 times analysis and same quantity shall be retained as control sample with proper labeling.
4.5.14        Insert the sampling rod in the container so as to take the sample from top, middle and bottom layer of the container. Collect the material on bio-shield paper (butter paper) for visual observation.
4.5.15        If there is no physical heterogeneity, mix the top, middle and bottom portion and transfer the required sampled material for preparing composite sample in polybag and  Label the polybag appropriately with GR No. Batch No., Etc.
4.5.16        Close the polybag with plastic cable ties under RLAF and likewise, carry out sampling for all subsequent container(s) of same batch.
4.5.17        Affix self-adhesive label of “SAMPLED”.   Refer Annexure - 7 to each container and close the container properly with cable tie.
4.5.18        Mix pooled sample drawn from individual container, which is collected in polybag for preparing sample for analysis and control sample by shaking vigorously. Then take out the required quantity of composite sample for analysis and control sample separately as per sample quantity list, in amber bottles. Procedure for preparation of sampling bottles is given in SOP 
/113 . 
4.5.19        Close the lid of the sampled bottles tightly; label shall be affixed on sampled bottles. (Refer Annexure - 7)
4.5.20        Send samples along with GRN, Bulk inspection sheet and Manufacturers Certificate Of Analysis to Quality Control Laboratory for analysis.
4.5.21        Carryout cleaning of sampling room as per SOP.  and record the same in format no. K/QC/087. Enter the sampling details in ‘Sampling room operation log book.” in the format as mentioned in Annexure - 3.
4.5.22    Use always clean and dried amber coloured glass bottles with inner cap and ROPP screw caps for collecting samples.


             4.6.1     Sampler shall enter the Betalactum group manufacturing area as per Gowning procedure.  
             4.6.2    Sampling shall be done as per above procedure   mentioned in 4.5

             NOTE:  The sampling should be done either using free sample for Testing provided with the intact container by the manufacturer or from any one container.


4.7.1     Insert the S.S. sampling device / Thick glass tube in the container and withdraw the sample. Out of this take the required quantity for composite sample and Sample for Analysis . Put the remaining quantity in the same container and close it properly.
4.7.2     Affix self-adhesive label of “SAMPLED” to each sampled container.


NOTE:  1.    Cleaning is required after sampling of each RM.                                                   
2.          If subsequent batch is of same RM, minimum cleaning of the area is required i.e. with the dry duster
3.          If the subsequent batch is of different RM, ensure appropriate cleaning is done to avoid any cross-contamination.
4.          Change the uniform while sampling of different RMs

4.7.1          Remove the used gowns, which shall be kept in the plastic bin labeled as “USED GARMENTS TO BE CLEANED” and send it for washing in laundry.
4.7.2          Take out used sampling devices, which is kept in recycling bin labeled as “USED SAMPLING DEVICES - TO BE CLEANED”, and send it for washing in washing room.
4.7.3           Keep the dried utensils it in the sampling room and place it in cupboard / S.S. hanger with individual polybag or shrink-wrap with “CLEANED” status label for every utensil.


4.7.1          Executive – QC is responsible for distribution of sample for analysis in Chemical and Microbiology laboratory.
4.7.2            Executive – QC is responsible for sending samples for any approved outside laboratory for analysis (complete or partial with regards to biological, HPTLC, Crystallinity etc.)
4.7.3            Update the work allocation register accordingly.
4.7.4            Keep the control sample bottles as per the desired storage condition at pre-designated condition
eg. At Room temperature         à In cupboard placed in Control Sample Room.
          At refrigerator temperature à QC refrigerator.

4.8              ANALYSIS OF RM

4.9.1          Officer – QC is responsible for taking out green sheet / Format of RM analytical format kept in Chemical Lab. Fill in initial, information about RM details in the green Sheet / Format.
4.9.2          Plan & perform the analysis of RM as per specification, respective pharmacopoeia or in-house procedure.
4.9.3          Record the results in the respective green sheet / Format, attach all necessary reports of IR/ UV / HPLC / GC Chromatograms etc. Sign the document with date and submit to Executive – QC for review.


4.10.1.    Executive – QC is responsible for verifying the recorded results by Chemist - QC and review of the results against standard limits.
4.10.2.    Executive – QC is also responsible for collecting analytical results from the approved outside laboratory parties.

4.10.3.    Check, Review and Sign the green sheet / format, submitted by Chemist - QC and forward it to Head of the Department QC.
4.10.4.    Head of the Department – QC is responsible for final review and disposition of RM.
4.10.5.    Review the green sheet / Format in totality (along with all necessary attachments like IR / UV / HPLC / GC chromatograms etc.) and record the disposition of RM either APPROVED OR REJECTED.
4.10.6.    Fill in the necessary details of quantity released / rejected, retest date and signature of Authorised QC person in GRN.  Retain QC copy (2nd copy of GRN) and return rest of the copies duly signed, to Warehouse.
4.10.7.    Fill in the necessary details like status for approved / rejected, signature and date in RM Register.
4.10.8.    All materials must be released within 15days of received GRN date.
4.10.9.    In case of out of specification (OOS) results follow the SOP 


4.11.1      Chemist – QC to prepare APPROVED / REJECTED label as per the status of RM and maintain the reconciliation record of labels. Refer Annexure – 7 for format of Approved / Rejected label.
4.11.2      Sign on each label either approved or rejected and affix on each container by pasting over UNDER TEST zone of label.
4.11.3      Hand over approved / rejected GRN copies to Warehouse and advise Warehouse Personnel to transfer the RM container to the respective zone as per disposition. 


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