WAR-085 Sampling and Inspection of Raw and Bulk Materials

1.0 DOCUMENT OWNER

Warehouse / Quality Manager

2.0 PURPOSE

Detail the procedure for inspecting and sampling of receipted raw materials (RM); bulk materials (BM) or Semi-Finished goods (e.g. tablets, pastes, capsules) and active pharmaceutical ingredients (API) at GMP site.

3.0 SCOPE

Covers receipted RM, BM and API at the GMP site and contracted processing sites for manufacturing of pharmaceuticals.

4.0 RESPONSIBILITY \ BUSINESS RULES

Refer to section 6 for all definition and acronyms.

4.1 Only those trained in inspection and sampling can carry out these procedures.  The Warehouse Operators who are trained in sampling and inspection are termed as QA Sampling Inspectors.   

4.2 All RM, BM and API are sampled in the laminar flow booth located in the quarantine section of the receiving warehouse. When this booth is under maintenance, the laminar flow booth in the dispensary can also be used.

4.3 Only one lot of any item may be sampled at any one time with a cleaning step between lots.

4.4 Drugs of dependence or others covered by special security requirements are to be sampled in the presence of a witness. 

4.5 All RM, BM and API are sampled in accordance with sampling plans and sampling guidelines approved by Quality.

4.6 Lot dispositions (change from the initial Quarantine status to A, B, C, R or H status) for RM, BM and API are carried out by approved QUALITY personnel, based on C of A, Warehouse documents, NIR results and samples provided by QA Sampling Inspectors in the Warehouse.

4.7 Trained and authorized QA sampling inspectors in the Warehouse place lots in N status if specified in the RMSTR (Raw Material Specification – Test Report), unless quality disallow placing any specific item/lot or material from a given manufacturer or supplier in N status.

4.8 The sequence of sampling carried out in the Sampling Booth is as follows: 

Samples for microbiological testing are first drawn, followed by samples for chemical testing. The host material from where these samples are drawn is removed from the Sampling Booth and only then; NIR vials are filled in the Sampling Booth per requirement, from chemical samples already drawn.

4.9 Any re-sampling activity is carried out strictly in accordance with instructions from Quality.

4.10 All RM, BM and API deliveries are stored in appropriate areas before and after sampling. Physical transfers of material within the Warehouse are reflected in the ERP system (Enterprise Resource Planning Software) through prompt transfer transactions by Warehouse Operators in ERP system.

4.11 Warehouse QA Sampling Inspectors are responsible for checking and matching information contained in the “Form 850 – Inspection of Goods on Delivery” (Appendix B) for; container labels; Certificate of Analysis and RMSTR before sampling. Warehouse staff is responsible for filling out appropriate sections of RMSTR; for completing logbooks; carrying out sampling and carrying out NIR scans per quality requirements and for transferring the samples promptly to the quality Laboratory.

4.12 QA Sampling Inspectors are required to record any significant observation on documents they provide to the quality Laboratory along with samples to assist the quality Laboratory with appropriate scrutiny of received materials.

4.13 As soon as any delivery or parts thereof are placed in Q-hold status or Reject status, the QA Sampling Inspectors in the Warehouse shall assist in proper labelling of such items and prompt transfer of such items to the locked Q-hold cage or reject cage with appropriate transactions in ERP system.

4.14 All sampling transactions are promptly recorded in ERP system by QA Sampling Inspectors in the Warehouse.

4.15 QA Sampling Inspectors work closely with quality and Technical Services to carry out NIR analysis in the Warehouse and carry out requisite scheduled diagnostic tests.  All maintenance work and validations on the NIR is executed / supervised by Technical Services.  All NIR scan results are checked and used by quality.

4.16 QA sampling inspectors in the warehouse authorized and trained to place lots in N Status in ERP system proceed to do so as outlined in Section 5.4.

5.0 PROCEDURE

5.1 Check the Delivered RM / BM / API Delivery and Plan the Sampling Activity

5.1.1 Check the “Form 850 – Inspection of Goods on Delivery” (Appendix B) paperwork for the item / lot that is filled in by the receiving store person. Locate the delivered lot in the receiving area and inspect the labels on the containers. Match these with details of permitted suppliers and manufacturers in the RMSTR for the given RM, BM or API. If there is a mismatch, contact quality immediately and stop all subsequent sampling activity for the delivery until issues are satisfactorily clarified by quality.

5.1.2 Check labels on containers and match details of description, grade, lot number, expiry date with Certificate of Analysis from the manufacturer.

5.1.3 Print the applicable pages of the RMSTR from the secured shared drive and note the sampling requirements. Note details of sample quantity, requirement for microbiological and NIR samples.

5.1.4 Check the MSDS for the item and note the special requirements for protective wear during sampling (refer SOP EHS-125 “Selection of Personal Protective Equipment”).  If clarifications are required, contact the Warehouse Manager or Environmental Health and Safety (EHS) representative.

5.1.5 Locate the sampling / inspection files for the given item in the Sampling Office in the Warehouse. Record the sampling level / plan to be used for any given lot of RM on the history chart for the given item / given supplier based on the quality Laboratory’s instructions. The quality Laboratory would specify the use of normal or reduced or tightened sampling plans based on the results of the analytical results of previous lots for the item / for the supplier or to satisfy any special requirements. If clarifications are required regarding sampling levels, contact the Laboratory Team Leader or Manager.

5.1.6 Check if a given delivery is for evaluation (look for “Evaluation” labels). Always check with the quality Laboratory and the Technical Services Department for special sampling instructions in the case of Evaluation materials.

5.1.7 Every container of all API deliveries is to be sampled.

5.1.8 Locate sampling plans; reduced / normal / tightened. It is to be noted that the first delivery of a given RM item from any manufacturer is always on a tightened sampling plan.

5.1.9 Note the number of containers in the delivery of an RM. Consult the appropriate sampling plan to be used for the delivery per the advice of Quality.

5.1.10 From the number of containers in the delivery of an RM, using the appropriate sampling plan, note the number of containers to be sampled. For example, if a given RM from a supplier is on a reduced sampling plan, a delivery containing 50 bags would need 2 bags of the delivery to be opened for sampling.

5.1.11 For BM, refer to sampling plan to select the number of containers and for sampling quantity.

5.1.12 Sample every container of each lot of API and comply with any special instructions provided by Quality for any specific lot or delivery.

5.1.13 Check the quantity of sample to be drawn indicated on the RMSTR for a given RM.  If the sample quantity indicated is 40 grams, the total sample to be drawn for the lot is a minimum of 40gms. If 2 bags are to be sampled, per sampling plan, it is required to draw at least 20gms from each bag into separate sample containers for each of the two bags.  Quality would advise their specific requirements for testing of any item / lot as required.  The maximum sample quantity for any given RM is 3 times that in the RMSTR.

5.1.14 As API’s are very expensive, the RMSTR quantities are adhered to unless otherwise advised by Quality for specific reasons.

5.1.15 Ensure that the requisite containers of the lot to be sampled (for RM / BM / API) are placed on captive alloy or plastic pallets. At random, select the needed number of containers to be opened for sampling from amongst the delivered pallets and place them on pallets before attempting to take them into the Sampling Booth.

5.1.17 Collect the requisite sampling implements (e.g. sterile / certified clean:  spoons, ladles, spikes).  Check RMSTR / MSDS and select requisite safety apparel / breathing protection. Collect requisite sampling containers and related items (e.g. bottles, sterile containers, plastic bags, cable ties, plastic patches. Collect and organize other items that are essential for carrying out sampling (e.g. lint free cloth, 70% alcohol).

5.1.19 Ensure the requisite sampling implements are within the expiration period before use.

5.2 Documentation of Sampling and Sampling in the Sampling Booth

5.2.1 Inspect the Sampling Booth and the Sampling Booth logbook.  Ensure that the booth is clean and is ready for sampling. Turn on the laminar flow booth. Wait for 10 minutes before checking the readings in Step 5.2.2.

5.2.2 Read the RH and temperature gauges located on the laminar flow booth. Ensure that these are between 25-40% and below 25 deg C respectively. If the readings are outside the range, do not commence sampling. Contact Engineering for corrective actions.

5.2.3 Check if the airflow indicator on the Sampling Booth panel displays in the green zone (60-105 Pa) and the dust filter air gauge also indicates in the green zone (0-250Pa).  Check and ensure that the airflow indicator mounted just inside the Sampling Booth room entrance also reads between 12-50Pa. If all these readings are favourable, sampling can be undertaken in the Sampling Booth. Sampling is always carried out in the indicated zone of laminar flow within the Sampling Booth.

5.2.4 Fill out details of date received, Purchase order, site lot number, manufacturer’s lot number, supplier name, manufacturer’s name, quantity delivered, number of containers, inspection level, sample size, sample code number on the relevant sections of the RMSTR already printed per Step 5.1.2 above.

5.2.5 Collect appropriate sampling implements and containers including cable ties and safety apparel / breathing apparatus.  Print labels for sampling containers showing name of RM or BM or API, Site item number, Site lot number, manufacturer’s lot number and date.

5.2.6 Use ERP system to produce yellow “Sampled” labels to apply on containers of the delivery after sampling. These labels will display Site lot number, date, name of sampler and sequence of sample (e.g. 1 of 3, 2 of 3 and 3 of 3).

5.2.7 Check the labels on the containers of RM / BM / API once again before taking them into the Sampling Booth. Ensure that there is no conflicting information or damages.  Ensure that the items are on aluminium alloy or plastic pallets before attempting to take the items into the Sampling Booth.

5.2.8 Enter details of date / time / Site item / lot number in the Sampling Booth logbook and room status indication board. Wear a fresh set of disposable overalls, gloves, hair net, overshoes and appropriate breathing device for the item being sampled. Use a dedicated pallet trolley to take the containers of the delivery being sampled. Clean the outside of drums / containers if they are not clean.

5.2.9 Organize requisite sampling implements, containers, labels, cable ties, plastic patches, adhesive tape and pen to take into the Sampling Booth. Count the items taken in to ensure that these can be completely accounted for at the end.

5.2.10 Use clean sampling devices (labelled “OK to Use”) for chemical sampling and sterile sampling devices (sealed in Sterile bags and signed and dated by the Quality Laboratory) for aseptic sampling. (Cleaning and labelling of these implements are carried out in accordance with WAR-105 “Cleaning of Sampling Booths and Implements in the Raw-Materials Quarantine Store.). Use ladles to withdraw liquid samples from drums; spoon or spatula to withdraw powder samples from drums, opened bags / cartons; use spikes for withdrawing powder samples from unopened bags.

5.2.11 Before actually sampling, check if the delivered material has been properly sealed and there are no breaches to the primary packaging holding the contents. Observe the material for particle size, crystalline or amorphous nature, for flakes, for colour, variations of the same and for foreign objects or specks and for uniformity and consistency. If any observations are made that are inconsistent with the description in the RMSTR or out of the normal, contact Quality immediately and do not proceed with sampling until the issues are examined. A Quality representative would assist by entering the booth and inspecting the item.

5.2.12 Carrying out aseptic sampling of a powder from a closed bag, spray 70% alcohol on to a small area of the outside of the bag containing the powder, wipe with a clean cloth.  Spray your disposable rubber gloves with 70% alcohol and allow to air dry. Remove a sterile sampling spike/spatula/spoon from the autoclave bag and insert it into the bag containing the powder. Draw the sample and place the sample into a sterile container and close the lid of the sample container promptly. Weigh the sample drawn in the balance available in the Sampling Booth and note the weight of the sample drawn. This sample quantity is entered as sample transaction in ERP system at a ERP system console by the QA Sampling Inspector once sampling is completed (Step 5.3.2).

5.2.13 Seal the area of the bag containing the powder where the spike was introduced, with a polyethylene patch and seal the patch to the outside of the bag with adhesive tape / patch so that only polyethylene patch contacts the powder held in the bag. Apply a yellow “Sampled” label to the bag of powder from where the sample was drawn.

5.2.14 The procedure for drawing aseptic liquid sample or powder sample from an open drum, bag or container in the Sampling Booth is similar. Spray the disposable gloves with 70% alcohol, allow to air dry before withdrawing the sterile sampling implement from the sterile bag and withdrawing the sample. Place the samples quickly in sterile containers; seal the sample containers and the containers from where the samples were drawn.  Promptly label all the containers with sample / sampling details.

5.2.15 Chemical samples are drawn using sampling implements that are clean (labelled “OK to Use”) and placed in non aseptic sampling containers but the process is essentially the same as described for aseptic sampling. The containers being sampled are always placed between the Operator and the inlet face of the Sampling Booth. Sampling is done carefully to limit any spillage or dusting.

5.2.16 Once sampling is carried out, check again that all the containers are sealed. Collect all the used sampling implements; place them in a plastic bag after wiping them clean of visible residue with 70% alcohol and clean cloth. Collect all sample containers and take them out of the Sampling Booth. Clean the outside of the containers of RM / BM / API recently sampled with a clean cloth and dispose all the used cleaning cloths in the S4 waste bin. Vacuum the outside of the containers / pallets of any spills and wipe the pallets with 70% alcohol to remove any spills before removing the pallet with containers out of the Sampling Booth.

5.2.17 If NIR samples are required (this will be specified in the RMSTR), ensure that the source containers of the RM / BM / API have been removed from the Sampling Booth.  Take the recently drawn chemical samples back into the Sampling Booth with a specific number of empty NIR vials and fill the NIR vials with material drawn from the chemical samples. Re-seal the chemical sample containers and the NIR vials. Record the details in the Sampling Booth logbook to denote the end of sampling.

5.2.18 Clean the Sampling Booth per SOP WAR 105 “Cleaning the Sampling Booth and Implements in the Raw Material Quarantine Store” and record cleaning start and end times in the logbook Cleaning verification is carried out and recorded in the logbook. The Sampling Booth is then marked “Clean” on the display board outside and is ready for the next sampling activity.

5.2.19 After the sampling, put away the containers of RM / BM / API into the appropriate areas in the Warehouse.

5.2.20 If quality require a Deviation Report for any given item / lot due to planned or unplanned deviations, QA Sampling Inspectors assist in preparation of a Deviation (QMS-035 Pharmaceutical Deviation Report System”).

5.3 Complete Sampling Documentation and ERP System Entries

5.3.1 Record details of sample date, Site lot number, manufacturer’s lot number, description of material and inspection level and your signature in the sampling history chart for the item in the item file.

5.3.2 Log on to ERP System using your personal sign on and password. Input sampling details with quantity of samples drawn. Ensure that the correct inventory units of measure are used (e.g. grams, Thousands, number). Ensure that you confirm in ERP System that sampling is completed for the given lot.

5.3.3 Complete the requisite sections of the RMSTR. Attach the same to a copy of the “Form 850 – Inspection of Goods on Delivery” (Appendix B) after signing the sampling section. Attach the Certificate of Analysis for the lot from the manufacturer and the aseptic and chemical samples drawn.  Ensure that the labels on the samples are correct. If NIR samples are involved, proceed to analyse the NIR vials in the NIR instrument located in the QA Sampling Inspector’s office as per Step 5.4. The NIR results have to be attached to the samples before the samples and documents are submitted to the Quality Laboratory.

5.4 NIR Scanning, Placement of Lot in N status and Sample Submission to the Quality Laboratory

5.4.1 Carry out NIR scanning of the samples drawn in accordance with appropriate SOP Attach the printed ID report, along with documents in Step 5.3.3.

5.4.2 Dispose the NIR vials with their contents into the S4 sharps bin placed conveniently in the office.

5.4.3 Review Appearance and NIR ID results. Record appearance and NIR ID details on RMSTR in the relevant sections. Review Certificate of Analysis from manufacturer/Supplier for the lot against RMSTR. If no mismatch is noticed, sign in the relevant section of RMSTR to confirm that you have reviewed the Certificate of Analysis. If you have noticed a mismatch or have reservations, record your comments.

5.4.4 If the Appearance, NIR ID and Certificate of Analysis comply with RMSTR, proceed to place the lot in N Status in ERP System in accordance with SOP “Lot Disposition”. Ensure first that there is no note from QUALITY in the file, directing you not to place a given item or lot from the supplier/manufacturer in N status. Check with Quality if any clarifications are required. Then, Place the lot in N status in ERP System.

5.4.5 If any of the three, namely Appearance, NIR ID or Certificate of Analysis do not match RMSTR or if you have any other reservations, do NOT place the lot in N status. Record details of non-compliance or comments in the RMSTR and record comments in “Form 855 – OOS Verification for Raw Material Identification Using NIR” (Appendix C).

5.4.6 Attach the NIR ID details with lab samples, RMSTR and Certificate of Analysis along with “Form 850 – Inspection of Goods on Delivery” (Appendix B) and “Form 855 – OOS Verification for Raw Material Identification Using NIR” (Appendix C). where applicable for the receipted lot.

5.4.7 Submit all the attachments and the samples to the QUALITY Laboratory after entering sample details in the QC sample logbook.

5.5 Labelling and Re-Location of Containers of RM / BM / API After Lot Disposition by Quality

5.5.1 Quality communicate lot dispositions of any given lot to Warehouse to enable labelling and storage in an appropriate location within the Warehouse and also update sampling plans to be used in future.

5.5.2 Quality change lot status in ERP System from Q to different Quality statuses. Status labelling is carried out in accordance with SOP “Material Status Indication”.

5.5.3 In the case of RM and API, Warehouse does not have to apply status labels to denote a change from Q to A, B or N status. H status and R status labels are promptly applied by Quality and Warehouse Operators relocate these containers to locked Q-hold cage and Locked reject cage respectively.

5.5.4 Promptly reflect all physical movements in ERP SYSTEM through appropriate transfer transactions.

Appendix A: Flowchart for Process

Appendix B: Form: Inspection of Goods on Delivery

Appendix C: Form: OOS Verification for Raw Material ID Using NIR

6.0        DEFINITIONS   / ACRONYMS   

API       Active Pharmaceutical Ingredients that have chemical activity and are the main therapeutically active agents. Examples include Prazosin Hydrochloride, Sildenafil Citrate or Amlodipine Besylate)

BM       Bulk Materials. They are also called Semi Finished Goods. These Include tablets, capsules, pastes, vials with biological or chemical activity.

EHS     Environmental Health and Safety

ERP System     Manufacturing, Accounting, & Planning System

MSDS  Material Safety Data Sheet

NIR       Near Infrared

QA       Quality Assurance

RH        Relative Humidity

RM       Raw Materials. Includes additives, diluents, binders, disintegrants, lubricants, coating agents or colors; (e.g. starch, Magnesium Stearate, Opadry white, Microcrystalline cellulose, Sodium Lauryl Sulphate).

RMSTR     Raw Material Specification – Test Report

ERP     Enterprise Resource Planning