Controls available to avoid Cross Contamination in Manufacturing Area

2.      OFCB with laminar flow, HEPA filtered air.

3.      Pressure Difference between working zone and cubical.

4.      Safe Working Zone defined for operation.

5.      Change of pallets (WH Pallets to Production Pallets).

6.      De-dusting of RM containers in Pallet Change Area.

7.      Segregated storage of RM containers in Day Store.

8.      Line Clearance for Dispensing Area, Accessories like containers, scoops, balance by Production & QA.

9.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

10.   General/complete cleaning performed after every batch.

11.   Over gowning before starting operation.

12.   Dispensing of only one material at a time.

13.   Change of scoop after each weighing.

14.   Intense color & fluffy material dispensing at the end of excipients dispensing.

15.   Use of fresh gowning before starting next product dispensing.

16.   API dispensing at last.

17.   Two labels for each weighed material.

18.   Tamperproof red tag identification for each dispensed API.

19.   Designated area for storage of Dispensed RM i.e. Batch Staging area.

20.   Batch Staging: Batch wise segregation of dispensed batches.

21.   Area is kept under lock.

(Continued)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification done for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Verification by supervisor during API addition.

10.   Material reconciliation after unit operations/sub operations.

11.   Dry cleaning of external surface of IBC/Bins, before taking out of sifting area for blending operation with appropriate labelling.

12.   Storage of lubricated blend in designated area i.e. blend store area in close condition   with appropriate labels.

13.   Batch wise segregation of batches in Blend store area.

14.   Material collected for IPC is not added to batch & it is sent for destruction.

(Continued)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Verification by supervisor during API addition, wet granulation & drying parameter setting, blending activities.

10.   Material reconciliation after unit operation/sub operation.

11.   Dry cleaning of IBC/Bin before taking out of granulation area for blending operation with appropriate Labelling.

12.   Storage of lubricated blend in designated area i.e. blend store area in close condition with appropriate labels.

13.   Batch wise segregation of batches in Blend store area.

14.   Material collected for IPC is not added to batch & it is sent for destruction.

15.   Use of product dedicated finger bag for FBD, vent filters for RMG, silicon tubes for binder addition & hose pipes for material charging in Conta-blender.

(Continued)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Presence of supervisor during API addition, Wurster parameter setting, IPC & blending activities.

10.    Material reconciliation during processing.

11.    Dry cleaning of IBC/Bin before taking out of granulation area for blending operation with appropriate Labelling.

12.    Storage of lubricated pellets in designated area i.e. blend store area in close condition   with appropriate labels.

13.    Batch wise segregation of batches in Blend store area.

14.    Material collected for IPC is not added to batch & it is sent for destruction.

15.    Use of product dedicated finger bags & silicon tubes for spraying required for Wurster & hose pipes for material charging in Conta blender.

(Continued)

(Roll Compaction)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General/complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Material reconciliation during processing.

10.    Dry cleaning of IBC/Bin before taking out of granulation area for blending operation with appropriate Labelling.

11.    Storage of lubricated blend in designated area i.e. blend store area in close condition   with appropriate labels.

12.    Batch wise segregation of batches in Blend store area.

13.    Material collected for IPC is not added to batch & it is sent for destruction.

(Continued)

(used for Tacrolimus SDG)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Dry cleaning of IBC/Bin before taking out of granulation area for blending operation with appropriate Labelling.

10.    Storage of lubricated blend in designated area i.e. blend store area in close condition with appropriate labels.

11.    Batch wise segregation of batches in Blend store area.

12.    Material collected for IPC is not added to batch & it is sent for destruction.

13.    Dedicated area & equipment provided.

(Continued)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Change of gowning during product change over and end of shift.

9.      Presence of supervisor during API addition, Granulation, Spheronisation IPC & blending activities.

10.    Dry cleaning of IBC/Bin before taking out of granulation area for blending operation with appropriate labeling.

11.    Storage of lubricated pellets in designated area i.e. blends store area in close condition   with appropriate labels.

12.    Batch wise segregation of batches in Blend store area.

13.    Material collected for IPC is not added to batch & it is sent for destruction.

14.    Use of product dedicated finger bags & silicon tubes for spraying.

15.    Dedicated area & equipment provided for extrusion & Spheronisation.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Over gowning before starting operation.

7.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

8.      Dry cleaning of IBC/Bin is done before taking out of granulation area with appropriate labeling.

9.      Storage of lubricated pellets in designated area i.e. blend store area in close condition with appropriate labels.

10.    Batch wise segregation of batches in Blend store area.

11.    Material collected for IPC is not added to batch & it is sent for destruction.

12.    Presently area & equipment dedicated for Certain Products

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Blend verification for correctness.

7.      Punch verification & usage record.

8.      IPC samples are discarded and not added to batch.

9.      Dust cups facility for tooling to avoid oil contamination.

10.    Line clearance of the containers before use.

11.    Two labels for each storage containers.

12.    Provision of each container cleanliness checking on labels.

13.    Usage of single use poly bags/fasteners/tags.

14.    Yield reconciliation at the end of activity.

15.    Online metal detectors.

16.    Dust extraction systems provided.

17.    Product dedicated tooling’s (i.e. Punches).

18.    Separate area for WIP batches (ready for coating/awaiting for inspection).

19.    Separate area for SFG (bulk product) storage under lock & key.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Coating materials verification for correctness.

7.      DP checks during line clearance.

8.      Storage of coated tablets in double polybags followed by closed containers.

9.      Two labels for each storage containers.

10.   Batch wise segregation during storage of WIP/SFG.

11.   Yield reconciliation at the end of activity.

12.   Product dedicated silicon tubing.

13.   Separate area for WIP batches (awaiting for inspection).

14.   Separate area for SFG (bulk product) storage under lock & key.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Line clearance of the containers before use.

7.      Empty capsule verification for correctness.

8.      IPC samples are not added to batch.

9.      Storage of filled capsules in double polybags followed by closed containers.

10.   Two labels for each storage containers.

11.   Usage of single use Poly bags/fasteners/tags.

12.   Provision of each container cleanliness checking on labels.

13.   Yield reconciliation at the end of activity.

14.   Online metal detectors.

15.   Dust extraction systems provided.

16.   Separate area for WIP batches (waiting for inspection).

17.   Separate area for SFG (bulk product) storage under lock & key.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Dispensed material verification for gross weight & dispensed label content against BMR entries.

7.      Presence of supervisor during initial parameter setting & verification & IPCs.

8.      Material reconciliation during processing.

9.      Dust collector system to avoid dusting.

10.   Provision of each container cleanliness checking on labels.

11.   Usage of single use fasteners/tags.

12.   Storage of banded capsules in designated area i.e. Tablet / Capsule store area in close condition with appropriate labels.

13.   Material collected for IPC is not added to batch & it is sent for destruction.

14.   Presently area & equipment dedicated for certain Range of product

15.   Gelatin solution is used within 24 hours of preparation.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Material verification for dispensed label content against BMR entries.

7.      Presence of supervisor during initial parameter setting & verification.

8.      Material reconciliation during processing.

9.      Dust collector system to avoid dusting.

10.   Provision of each container cleanliness checking on labels.

11.   Usage of single use fasteners/tags.

12.   Material collected for IPC is not added to batch & it is sent for destruction.

13.   100% inspection of product, 360 degree view with help of 4 cameras for identification of 2 colors & physical defects.

(Manual)

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      General / complete cleaning performed after every batch.

4.      Line clearance given by production & QA supervisors before start of every batch.

5.      One batch at a time, under process in a cubicle.

6.      Storage of inspected tablets/capsules in double polybags followed by closed containers.

7.      Two labels for each storage containers.

8.      Batch wise segregation during storage of WIP/SFG.

9.      Yield reconciliation at the end of activity.

10.   Separate area for SFG (bulk product) storage under lock & key.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      Before starting packaging operation cleaning and line clearance is performed for each equipment on the packaging line. Line clearance is done by Prod operator, verified by Prod supervisor and IPQA. The same is documented in the BPR.

4.      General /complete cleaning before start of the batch.

5.      One batch is packed at a time in one packaging line.

6.      In between two packaging lines physical partition is available.

7.      Packing materials are checked for correctness against the standard SAP code of material mentioned in the approved batch packing record and issued to packaging line by production supervisor; then counter checked by production operator and received in packaging line. The same is documented in the BPR.

8.      SFGs are checked for correctness against the standard Product name and Batch No. mentioned in the approved batch packing Record and issued to packaging line by production supervisor, the same is counter checked by production operator and received in packaging line. The same is documented in the BPR.

9.      Labeling of all equipment’s, accessories, In-process materials and area for proper identification during operation.

10.   Reconciliation of each packaging material is performed at end of the batch and recorded in the BPR.

11.   Each shipper / drum is labeled with product and batch details for identification.

12.   FG of different batches is physically segregated by using pallets / stretch wrapping.

13.   Bottle cleaning machine is used to air clean each and every bottle before the filling operation. In process check for bottle cleanliness is done at start and every 30 minutes. During the packaging operation and recorded in the BPR.

14.   In bottle filing machine all product contact parts are easily detachable from the machine and easy to clean.

15.   In process check for cap cleanliness is done at start and every 30 minutes during the packaging operation and recorded in the BPR.

16.   Before going into the secondary packing area each and every bottles are induction sealed on-line with the help of induction sealer. In process check for Induction sealing quality is done at start and every 30 minutes during the packaging operation and recorded in the BPR.

17.   100% inspection of Barcode on bottle label is performed on-line by barcode reader. Challenge test for barcode reader performance is done at start and every 4 hr. during the packaging operation and recorded in the BPR.

18.   Before loading the bottle label roll on labeling m/c, specimen label for each roll is attached BPR and SAP code of specimen label is checked and counter checked by production person against the standard SAP code of material mentioned in the approved batch packing Record.

19.   SAP code of specimen sample for each AR No. of leaflet and Medication guide is checked and counter checked by production person against the standard SAP code of material mentioned in the approved batch packing Record. The same is attached to BPR.

2.      Production cubicles are maintained ‘negative pressure’ with respect to corridors.

3.      Before starting packaging operation cleaning and line clearance is performed for each equipment on the packaging line. Line clearance is done by Prod operator, verified by Prod supervisor and IPQA. The same is documented in the BPR.

4.      General /complete cleaning before start of the batch.

5.      One batch is packed at a time in one packaging line.

6.      In between two packaging lines physical partition is available.

7.      Packing materials are checked for correctness against the standard SAP code of material mentioned in the approved batch packing record and issued to packaging line by production supervisor; then counter checked by production operator and received in packaging line. The same is documented in the BPR.

8.      SFGs are checked for correctness against the standard Product name and Batch No. mentioned in the approved batch packing Record and issued to packaging line by production supervisor, the same is counter checked by production operator and received in packaging line. The same is documented in the BPR.

9.      Labeling of all equipment’s, accessories, In-process materials and area for proper identification during operation.

10.   Reconciliation of each packaging material is performed at end of the batch and recorded in the BPR.

11.   Each shipper / drum is labeled with product and batch details for identification.

12.   FG of different batches is physically segregated by using pallets / stretch wrapping.

13.   Before loading the foil roll on blister pack m/c, specimen of foil for each roll is attached BPR and SAP code of specimen of foil is checked and counter checked by production person against the standard SAP code of material mentioned in the approved batch packing Record.

14.   100% inspection of Pharmacode on foil is performed on-line by Pharmacode reader. Challenge test for Pharmacode reader performance is done at start and every 4 hr. during the packaging operation and recorded in the BPR.

15.   100% inspection of the product feed in the blister pockets is performed on-line by camera system.

16.   SAP code of specimen sample for each AR No. of Cartons, leaflets and Medication guides is checked and counter checked by production person against the standard SAP code of material mentioned in the approved batch packing Record. The same is attached to BPR.

17.   100% inspection of Pharmacode on carton and leaflet is performed on-line by Pharmacode reader. Challenge test for Pharmacode reader performance is done at start and every 4 hrs. during the packaging operation and recorded in the BPR.

2.      Before starting packaging operation cleaning and line clearance is performed for the packaging area. Line clearance is done by Prod operator, verified by Prod supervisor and IPQA. The same is documented in the BPR.

3.      One batch is packed at a time in one packaging area.

4.      Packing materials are checked for correctness against the standard SAP code of material mentioned in the approved batch packing record and issued to packaging line by production supervisor; then counter checked by production operator and received in packaging line. The same is documented in the BPR.

5.      SFGs are checked for correctness against the standard Product name and Batch No. mentioned in the approved batch packing Record and issued to packaging line by production supervisor, the same is counter checked by production operator and received in packaging line. The same is documented in the BPR.

6.      Labelling of all In-process materials and area for proper identification during operation.

7.      Reconciliation of each packaging material is performed at end of the batch and recorded in the BPR.

8.      Each drum is labelled with product and batch details for identification.

9.      FG of different batches is physically segregated by using pallets / stretch wrapping