| Line Clearance |
1.0 OBJECTIVE To lay down the procedure to ensure that the area and equipment, required for the dispensing, manufacturing and packing activities of pharmaceutical products are free from any potential sources of cross contamination/mix-ups. 2.0 SCOPE This procedure is applicable to the activities related to dispensing, manufacturing, packaging and related activities. 3.0 RESPONSIBILITY • Officer/Executive-Warehouse/Production • Officer/ Executive-In-Process Quality Assurance (IPQA) 4.0 ACCOUNTABILITY • Head Concerned Department • Head Quality / QA 5.0 PROCEDURE 5.1 Line Clearance is system for assuring that equipment and workstation are clean and free from any material, product, product residues and documents which are not required for current operation and the area is ready for the required operation to avoid cross contamination. 5.2 Line clearance shall be performed to check and ensure the cleanliness of the respective area and equipment for next stage / operation to be carried out. 5.3 All line clearance checks shall be included before each stage in BMR and BPR by the QA person. 5.4 Product specific requirements shall be mentioned in the checklist & shall be followed strictly during the line clearance. 5.5 Following shall be verified during line clearance: • Cleaned label is affixed on the equipment • Area status label is updated • Equipment log for individual equipment is updated with previous product stoppage & machine cleaning details • Area cleaning record is updated • In process product is released • BMR/BPR is updated up to the last stage • Ensure that Environmental conditions and pressure differential of the processing areas are within the limit • Door interlocking is working 5.6 In addition of above, before startup of activity, production & IPQA officer shall verify the checkpoints as per the batch manufacturing record (BMR)/batch packing record (BPR). 5.7 During line clearance, if any discrepancy observed, the production supervisor shall intimate for same & after rectification again line clearance check shall be performed. 5.8 Production officer shall perform the line clearance checks & record the observation in BMR/BPR or in the line clearance checklist (if applicable) in respective columns. If complies mark ‘√’, if does not complies mark ‘X’ and if not applicable write ‘NA’ in the respective line clearance columns and shall inform IPQA person for line clearance. 5.9 IPQA person shall check and ensure that all the parameters mentioned below (and as mentioned in respective stages of BMR/BPR) are within the limit. • Status label of the area. • Cleanliness of the area. It should be visually clean. • Status label of the equipment. • Dispensed Material contains AR No. similar on Dispensing Slip & Dispensing Tags • Cleanliness of the equipment. It should be visually clean. • Completion of the documents up to the stage. • Completion of the equipment log book up to the stage. • Environmental controls (Relative Humidity, Temperature, Differential pressure) are within the limit. • Complete removal of the previous product / batch from the respective area. • Swab test results (if any). • Appropriate calibration status on various equipments of the area. • COA of previous stage (if any). • COA of any material (if any). • Approved label (if any) on the material / product. • Gowning of person involved in the operation is appropriate and clean. • Issuance of the accessories required for the operation. 5.10 After satisfactory observation, line clearance shall be given for respective area by signing in the respective column of line clearance checklist of BMR/BPR. To Read this SOP Click here SOP for Starting Material Non-Conformance/Discrepancy Intimation. 5.11 During the line clearance of Dispensing Area / Activity, following checks shall be performed but not limited to: 5.11.1 Ensure that dispensing of API/excipients/solvents/primary/ secondary packing material carried out in their dedicated area. 5.11.2 Differential Pressure across pre-filters, Fine filter, HEPA filters and RLAF are within limits in case of API/excipients/solvents. 5.11.3 Ensure cleanliness of area, cleanliness of balances, calibration of balances, cleanliness of supply air grills of RLAF unit, cleanliness of return air grills of RLAF unit, and status label on IPC/bin/ balances/dispensing tools. 5.11.4 FIFO/FEFO (first in first out/first expires first out) is followed for starting material. 5.11.5 Adequate dispensing tools & utensils along with cleaned polybags / IPC is available. 5.11.6 Any loose container shall have appropriate label on it. 5.11.7 Vacuum cleaner is cleaned and its record is updated. 5.12 During the line clearance of any Manufacturing Equipment, following checks shall be performed but not limited to: 5.12.1 Ensure the absence of batch documents; labels, materials, powder or any remnants of previous product or batch and traces of water on each dismantle part of the equipment. 5.12.2 Weighing balances of each area shall be cleaned and calibrated as per their frequency & record is maintained. 5.12.3 Check the respective area and equipment as per the details mentioned in the BMR. 5.12.4 During cleaning verification gaskets, seals, valves, internal parts of pipes, pores & perforations shall be verified to ensure there are no stains or remnants of previous products. 5.12.5 Equipments cleanliness shall be verified in dismantled condition. 5.13 During the line clearance of Primary / Secondary Packing, following checks shall be performed but not limited to: 5.13.1 Ensure that the overprinting stereos of previous product or batch are removed from the machine / area and record is updated in production department. 5.13.2 Ensure the absence of batch documents; labels, materials, powder, strips, blisters or any remnants of previous product or batch and traces of oil/water on dismantle part of equipment or surrounding the equipment. 5.13.3 Upon first time preparation of the checklist, its version number shall be given as ‘00’ and after subsequent revision it shall be given sequentially as 01, 02, 03………and so on. Note: The entire cleaned labels shall be attached to the BMR/BPR. To Read this SOP Click here SOP for Responsibility of IPQA Personnel. 5.14 Type A Cleaning: 5.14.1 Type A cleaning is defined as the dry cleaning of the area and equipment, where there is change over for same product with different batch. Here the cleaning shall be done to remove the previous product remnants qualitatively. 5.14.2 Same products, stands for those products which are similar in formulation qualitatively. 5.15 Type B Cleaning: 5.15.1 Type B cleaning is defined as the wet cleaning of area & equipments, where there is change over from one product to another product. Here the cleaning is done to complete removal of previous product remnants quantitatively. The equipment and area stands visually clean. 5.15.2 Another product stands for those products which are different in formulation as below: • Different API • Same API but different excipients • Different in colours and flavors 5.16 In case the product formulation is similar qualitatively, but the product strength is different then • Type A cleaning shall be performed while change over from lower strength to higher strength. • Type B cleaning shall be performed while change over from higher strength to lower strength. 5.17 Type B cleaning shall be performed, if cleaning validity of area and equipment exceeds the hold time period. 5.18 Type A cleaning shall be performed before usage of area and equipments (within hold time period), if area and equipment is not used within 24 hours of Type B cleaning. 5.19 Cleaning shall be performed on daily basis of area and equipment in dry powder injection at the end of shift. |
