Standard Operating Procedure (SOP) for Review of Batch Manufacturing Record (BMR) and Batch Packing Record (BPR) in the pharmaceutical manufacturing plant. A detailed checklist for review of BMR and BPR for Draft Copy as well as Filled Copy of Batch Manufacturing/Packing Records.
Procedure for BMR & BPR Review
1.0 PURPOSE:
- The purpose of this SOP is to define the procedure to review the draft Batch Manufacturing Record (BMR) and Batch Packing Record (BPR) prior to final approval. Also, this SOP shall be applicable for a review of executed BMR/BPR prior to the final release of batches.
2.0 SCOPE:
- Scope of this SOP covers for the review of the draft as well as filled Batch Manufacturing Record (BMR) and Batch Packing Record (BPR) at the pharmaceutical manufacturing plant.
3.0 REFERENCES:
- In-house
4.0 RESPONSIBILITY:
- The user department shall be responsible for the preparation of draft BMR/BPR and shall handover toBMR – BPR – REVIEW QA for review along with the intended supporting documents
- QA designee shall be responsible for the review of draft Batch Manufacturing Record (BMR) as well as Batch Packing Record (BPR) as per Annexure-1 and Annexure-2.
- QA/Production shall be responsible for the review of filled Batch Manufacturing Record (BMR) as well as Batch Packing Record (BPR) as per Annexure-3 and Annexure-4.
- HOD of Production and HOD of Packing shall be responsible for the review of draft BMR/BPR and subsequent approval of BMR/BPR.
- QA Head shall be responsible for final approval of master BMR/BPR as well as compliance of SOP.
5.0 ABBREVIATIONS USED IN SOP FOR BMR, BPR REVIEW:
- AR. No. : Analytical Report Number
- ADD: Analytical Development Department
- BMR: Batch Manufacturing Record
- BOM: Bill of Material
- BPR: Batch Packing Record
- COA: Certificate of Analysis
- Dept: Department
- ERP: Enterprise Resource Planning
- FDD: Formulation Development Department
- IH: In House
- IMO: Issue Material Order
- MPS: Master Product Specification
- PDD: Packaging Development Department
- QC: Quality Control
6.0 PROCEDURE FOR REVIEW OF BMR AND BPR:
- Review of Draft Batch Manufacturing Record (BMR) and Batch Packing Record (BPR):
- Concern production officer/Packing officer shall handover draft BMR/BPR to QA for review along with the intended supporting documents.
- QA shall review draft BMR/BPR as per Annexure-1 and Annexure-2 respectively and shall return to concern production officer for correction.
- Concern production officer/Packing officer shall correct the BMR/BPR and shall return to QA for the final review. After satisfactory review of draft copy, final print shall be taken for approval
- All persons involved in the review of draft BMR/BPR shall ensure to compliance against the checkpoints as per subsequent Annexure-1 and Annexure-2.
- All concerns involved in the review shall go through the checkpoints as a part of training and shall provide the acknowledgment as per Annexure-1 and Annexure-2 for their understanding and future compliance.
- QA shall issue a working copy of Annexure-1 and Annexure-2 to the respective person involved in draft BMR/BPR review as a ready reference.
- The master copy shall be kept with QA and filed with a master copy.
- Any amendment to the checklist shall be done with the help of change control and the revised checklist for review of draft BMR/BPR shall again reissue to the concerned person.
- QA shall also ensure the retrieval of issued Annexure-1and Annexure-2 controlled copy and the same shall be destroyed.
- A retired signed copy shall be retrieved by QA prior to the issuance of the checklist.
- Review of Filled Batch Manufacturing Record (BMR):
- Production officer shall handover filled BMR to QA after proper checking and signing in place of approved production chemist in BMR.
- QA shall review filled BMR as per Annexure-3 & in case of any discrepancies to checklist or some other discrepancies observed and shall be documented in Executed Batch Record Review Sheet as per Annexure-5.
- If any discrepancies observed against standard/limit as per BMR shall be recorded in the history sheet of respective BMR and shall be investigated prior to the further course of action.
- Review of Filled Batch Packing Record (BPR) :
- The packing officer shall handover filled BPR to QA after proper checking and signing in place of approved Packing Head/ Approved Production Head in BPR.
- QA person shall review filled BPR as per Annexure-4 and in case of any discrepancies to checklist or some other discrepancies observed and shall be documented in Executed Batch Record Review Sheet as per Annexure-5.
- If any discrepancies observed against standard/limit as per BPR shall be recorded in the history sheet of respective BPR and shall be investigated prior to the further course of action.
- Review of Batch Manufacturing Record (BMR) and Batch Packing Record after Packing:
- Ensure the first page of BMR/BPR is filled and ensure that the data/information provided on the cover page of BMR/BPR is correct.
7.0 ANNEXURES / CHECKLIST FOR BMR REVIEW:
Annexure 1: Checklist for Draft BMR Review.
| Sr. No. | Check Points | Reference Documents |
| STEP 1: INTRODUCTION OF NEW PRODUCT (BMR Review) | ||
| 1 | Ensure that the availability of Approved MPS. | Approved MPS |
| 2 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 3 | Ensure that the availability of the Approved Bill of Material Master. | Approved BOM |
| 4 | Ensure that the availability of Risk Assessment Report of Granulation/ Compression and Coating (as required). | SOP Approved MPS |
| 5 | License no, Form no, Generic name, Product name (Brand name) and Label Claim/Category, product strength and type of dosages form. | FDA License copy |
| 6 | Product Code, Description, Batch Size, BOM Code, Unit, Item Code, Item Ref. Lot, Item Name/Manufacturer Code, Quantity (Lot Wise), Material Potency, Minimum potency, Adjust potency, BOM valid up to and BMR version No. | Approved MPS Approved BOM |
| 7 | Product Shelf Life. | Approved MPS |
| 8 | Product stability data. | Approved MPS |
| Product description (core tablet /coated tablet /finished product specification). | Approved MPS | |
| 9 | Grade (Pharmacopoeial status) of API and Excipients. | Approved MPS Master BOM |
| 10 | Overages in Raw materials added, (if any) | Approved MPS |
| 11 | Product manufacturing and packing special precautions (if any). (e.g. Light Sensitive and Hygroscopic) | Approved MPS |
| 12 | Stage wise yield limits. | IH |
| 13 | Bill of Material/Work order, pages, and space for entries/ instructions and UOM (Unit of Measurement) | NA |
| 14 | Details of product equipment’s/utensils are used for manufacturing. | IH |
| 15 | Equipment equivalency and occupancy as per batch size | IH/SOP |
| 16 | Item codes for raw materials as per regulated /non- regulated market requirement | Approved BOM |
| 17 | Details of environmental conditions for product stage wise. | Approved MPS |
| 18 | During Sifting and Milling process checks and ensures Mesh size/ Screen size/ Co-sifting / Pre-mixing/Qty. and Ingredients used. | Approved MPS |
| 19 | During Binder Preparation process checks and ensures Sieve/Binder preparation time and Temperature of Purified Water. | Approved MPS |
| 20 | During Mixing and Granulation processes checks and ensure Material sequence/ Mixing time/ Agitator -Chopper speed and Ampere load. | Approved MPS |
| 21 | During Drying process checks and ensure Operating parameters/ LOD/Total drying time. | Approved MPS |
| 22 | During Sizing and Milling checks and ensure Screen size/Mesh size/ Direction of blades / Speed and Milling time. | Approved MPS |
| 23 | During Lubrication (Blending) checks and ensure Blending time / Speed and LOD. | Approved MPS |
| 24 | During Compression and Inspection checks and ensure Physical parameters / Operating parameters/ Punch description (Drawing) /Tablet description, dimension / Machine type/ Machine speed/ Qty. of defected tablets and Quantity of good tablets. | Approved MPS |
| 25 | During Coating and Inspection checks and ensure Physical parameters/ Operating parameters /Quantity/ Stirrer RPM / Time for milling/ Homogenization/ Qty. of defected tablets and Quantity of good tablets. | Approved MPS |
| 26 | Coating specifications like Appearance, Weight, Thickness, Diameter, DT, etc. shall be the part of BMR. | Approved MPS |
| STEP 2: SITE TRANSFER PRODUCT (BMR Review) | ||
| 1 | Ensure that the availability of Site Transfer BMR. | Approved BMR |
| 2 | Ensure that the availability of Approved Change Control. | Approved Change control |
| 3 | Ensure that the availability of the Approved Master Bill of Material. | Approved BOM |
| 4 | Ensure that the availability of Risk Assessment Report of Granulation/ Compression and Coating (as required). | IH/SOP |
| 5 | License no, Form no, Generic name, Product name (Brand name) and Label Claim/Category, product strength and type of dosages form. | FDA License |
| 6 | Product Code, Description, Batch Size, BOM Code, Unit, Item Code, Item Ref. Lot, Item Name/Manufacturer Code, Quantity (Lot Wise), Material Potency, Minimum potency, Adjust potency, BOM valid up to and BMR version No. | Approved BOM Approved BMR |
| 7 | Product Shelf Life. | Approved BMR |
| 8 | Product Stability Data. | Transfer Site |
| 9 | Product description (core tablet /coated tablet /finished product specification). | Approved BMR FP Specification |
| 10 | Batch size (Kg/No. of units), unit dosage weight/Lot division as per batch size/ Overages in Raw materials added, (if any) | Approved BOM Approved BMR |
| 11 | Grade (Pharmacopoeial status) of API and Excipients. | Approved BOM Approved BMR |
| 12 | Product manufacturing special precautions (if any). (e.g. Light Sensitive and Hygroscopic) | Approved BMR |
| 13 | Stage wise yield limits | IH |
| 14 | Bill of Material/Work order pages and space for entries/ instructions and UOM (Unit of Measurement) | NA |
| 15 | Details of product equipment’s/utensils are used for manufacturing. | IH |
| 16 | Equipment equivalency and occupancy as per batch size | IH/SOP |
| 17 | Item codes for raw materials as per regulated /non- regulated market requirement | Approved BOM Approved BMR |
| 18 | Product-related Stage wise Environmental Condition | Approved BMR |
| 19 | Ensure that the availability of Tooling Drawing/Change Part | IH |
| 20 | Ensure that the availability of the Site Product History/Flow Chart. | From Site |
| 21 | During Sifting and Milling process checks and ensures Mesh size/ Screen size/ Co-sifting / Pre-mixing/Qty. and Ingredients used. | Approved BMR |
| 22 | During Binder Preparation process checks and ensures Sieve/Binder preparation time and Temperature of Purified Water. | Approved BMR |
| 23 | During Mixing and Granulation processes checks and ensure Material sequence/ Mixing time/ Agitator -Chopper speed and Ampere load. | Approved BMR |
| 24 | During Drying process checks and ensures Operating parameters/ LOD/Total drying time. | Approved BMR |
| 25 | During Sizing and Milling checks and ensure Screen size/Mesh size/ Direction of blades / Speed and Milling time. | Approved BMR |
| 26 | During Lubrication (Blending) checks and ensure Blending time / Speed and LOD. | Approved BMR |
| 27 | During Compression and Inspection checks and ensure Physical parameters / Operating parameters/ Punch description (Drawing) /Tablet description, dimension / Machine type/ Machine speed/ Qty. of defected tablets and Quantity of good tablets. | Approved BMR |
| 28 | During Coating and Inspection checks and ensure Physical parameters/ Operating parameters /Quantity/ Stirrer RPM / Time for milling/ Homogenization/ Qty. of defected tablets and Quantity of good tablets. | Approved BMR |
| 29 | Coating specifications like Appearance, Weight, Thickness, Diameter, DT, etc. shall be the part of BMR. | Approved BMR |
| STEP 3: FORMULATION CHANGE | ||
| A. MAJOR CHANGE (E.G. GRANULATION PROCESS CHANGE) | ||
| 1 | Ensure that the availability of Approved MPS. | Approved MPS |
| 2 | Ensure that the availability of the Approved Master Bill of Material. | Approved BOM |
| 3 | Ensure that the availability of Approved Change Control. | Approved Change control |
| 4 | Ensure that the availability of Risk Assessment Report of Granulation/ Compression and Coating (as required). | IH/SOP |
| 5 | License no, Form no, Generic name, Product name (Brand name) and Label Claim/Category, product strength and type of dosages form. | FDA License |
| 6 | Product Code, Description, Batch Size, BOM Code, Unit, Item Code, Item Ref. Lot, Item Name/Manufacturer Code, Quantity (Lot Wise), Material Potency, Minimum potency, Adjust potency, BOM valid up to and BMR version No. | Approved MPS Approved BOM |
| 7 | Overages in Raw materials added, (if any) | MPS |
| 8 | Product Stability Data. | Approved MPS |
| 9 | Product Shelf Life. | Approved MPS |
| 10 | Grade (Pharmacopoeial status) of API and Excipients. | Approved BOM |
| 11 | Equipment equivalency and occupancy as per batch size | IH/SOP |
| 12 | Product description (core tablet /coated tablet /finished product specification). | Approved BMR |
| 13 | Bill of Material/Work order pages and space for entries/ instructions and UOM (Unit of Measurement) | NA |
| A. MINOR CHANGE (E.G. CHANGE IN QUANTITY) | ||
| 1 | Ensure that the availability of Approved MPS or Availability of supportive documents. | Approved MPS Supporting documents |
| 2 | Ensure that the availability of the Approved Master Bill of Material. | Approved BOM |
| 3 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 4 | License no, Form no, Generic name, Product name (Brand name) and Label Claim/Category, product strength and type of dosages form. | FDA License |
| 5 | Product Code, Description, Batch Size, BOM Code, Unit, Item Code, Item Ref. Lot, Item Name/Manufacturer Code, Quantity (Lot Wise), Material Potency, Minimum potency, Adjust potency, BOM valid up to and BMR version No. | Approved BOM |
| 6 | Overages in Raw materials added, (if any) | Approved MPS Existing BMR |
| 7 | Product Shelf Life. | Approved MPS Existing BMR |
| 8 | Grade (Pharmacopoeial status) of API and Excipients. | Approved BOM |
| 9 | Bill of Material/Work order: pages and space for entries/ instructions and UOM (Unit of Measurement) | NA |
| STEP 4: OTHER TYPE OF CHANGES | ||
| A. PHARMACOPOEIAL CHANGE | ||
| 1 | Ensure that the availability of the Approved Master Bill of Material. | Approved BOM |
| 2 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 3 | BMR version No. Master Bill of Material Code No. | Approved BOM |
| 4 | Pages and space for entries/ instructions /quantities and UOM | NA |
| B. BATCH SIZE CHANGE | ||
| 1 | Ensure that the availability of the Approved Master Bill of Material. | Approved BOM |
| 2 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 3 | FDD Approval required. | Supporting Document |
| 4 | Ensure that the availability of the Risk Assessment Report of Granulation/Compression/Coating stage. | NA |
| 5 | BMR version No. Master Bill of Material Code No. | Master BOM |
| 6 | Pages and space for entries/ instructions /quantities and UOM | NA |
| A. PUNCH SPECIFICATION CHANGE | ||
| 1 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 2 | FDD Approval required. | Supporting Document |
| 3 | BMR version No. | NA |
| 4 | Pages and space for entries/ instructions /quantities and UOM. | NA |
| B. COMPRESSION SPECIFICATION CHANGE | ||
| 1 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 2 | FDD Approval required. | Supporting Document |
| 3 | BMR version No. | NA |
| 4 | Pages and space for entries/ instructions /quantities and UOM | NA |
| C. CRITICAL PROCESS PARAMETER FREEZE | ||
| 1 | Ensure that the availability of Approved Change Control. | Approved Change Control |
| 2 | Approved Trend Data required. | NA |
| 3 | BMR version No. | NA |
| 4 | Pages and space for entries/ instructions /quantities and UOM | NA |
| ACKNOWLEDGEMENT: I______________________has read the above checkpoints which are required to ensure during review of draft BMR and understood the same. | |
| Name: | |
| Emp. Code: | |
| Department: | |
| Sign/Date: |
Annexure 2: Checklist for Draft BPR Review.
| Sr. No. | Check Points | Reference Documents |
| STEP 1: INTRODUCTION OF NEW PRODUCT | ||
| 1. | Ensure that the availability of Approved MPS. | NA |
| 2. | Ensure that the availability of Approved Change Control. | NA |
| 3. | Ensure that the availability of the Approved Master Bill of Material (PM). | NA |
| 4. | Ensure that the Risk Assessment Report (Packing) | MPS |
| 5. | Product name: Generic name, Brand name. | FDA License |
| 6. | Packing code, BPR version No. | Master BOM |
| 7. | Product strength, Type of dosage form & label claim/Category | FDA License |
| 8. | Stability Data/Finished Product Shelf Life | MPS |
| 9. | Description as per Finished Product Specification. | MPS |
| 10. | Product-related special precautions (if any) (e.g. Light Sensitive and Hygroscopic) | MPS |
| 11. | Environmental Condition | MPS |
| 12. | Product-Related Pack Profile | MPS |
| 13. | Packing Area for the product: Equipment’s used for Packing | IH |
| 14. | In-process test (Leak test, Morpholine test) | IH |
| 15. | Bill of Material/Work order: pages and space for entries/ instructions | NA |
| 16. | Yield limits (To be established) | IH |
| STEP 2: SITE TRANSFER PRODUCT | ||
| 1. | Ensure that the availability of Site Transfer BPR. | NA |
| 2. | Ensure that the availability of Approved Change Control. | NA |
| 3. | Ensure that the availability of the Approved Master Bill of Material (PM). | NA |
| 4. | Ensure that the availability of the Risk Assessment Report (Packing) | Transfer BPR |
| 5. | Product name: Generic name, Brand name. | FDA License |
| 6. | Packing code, BPR version No. | Master BOM |
| 7. | Product strength, Type of dosage form & label claim/Category | FDA License |
| 8. | Stability Data/Finished Product Shelf Life/Description | Transfer BPR |
| 9. | Product-related special precautions (if any) (e.g. Light Sensitive and Hygroscopic) | Transfer BPR |
| 10. | Environmental Condition/Pack Profile | Transfer BPR |
| 11. | Packing Area for the product: Equipment’s used for Packing | IH |
| 12. | In-process test (Leak test, Morpholine test) | IH |
| 13. | Bill of Material/Work order: pages and space for entries/ instructions | NA |
| 14. | Yield limits (To be established) | IH |
| 15. | Ensure that the availability of Change Part | From Site |
| STEP 3: CHANGE IN PACK STYLE | ||
| 1. | Ensure that the availability of stability data. | FDD |
| 2. | Ensure that the availability of Pack Profile. | PDD |
| 3. | Ensure that the availability of Approved Change Control. | NA |
| 4. | Ensure that the availability of the Approved Master Bill of Material (PM). | NA |
| 5. | Ensure that the Risk Assessment Report (Packing) | NA |
| 6. | Ensure that the availability of the Approved Master Bill of Material (PM). | NA |
| 7. | Ensure that the Risk Assessment Report (Packing) | NA |
| 8. | Packing code, BPR version No. | Master BOM |
| 9. | Bill of Material/Work order: pages and space for entries/ instructions | NA |
| 10. | Yield limits (To be established) | IH |
| STEP 4: PARAMETER FREEZE (Forming Roller Temp./Sealing Rolling Temp./Machine RPM/Compressed Air Pressure/ Yield data) | ||
| 1. | Ensure that the availability of Approved Change Control. | NA |
| 2. | Department Approved Trend Data required. | NA |
| 3. | BPR version No. | NA |
| 4. | Pages and space for entries/ instructions /quantities and UOM | NA |
| ACKNOWLEDGEMENT: I______________________has read the above checkpoints which are required to ensure during review of draft BPR and understood the same. | |
| Name: | |
| Emp. Code: | |
| Department: | |
| Sign/Date: |
Annexure 3: Checklist for Filled BMR Review.
| Stage Of Processing | Granulation/ Compression / Coating | |
| Sr. No. | Checkpoints | Complies/Not Complies/NA |
| 1 | Check all entries mentioned on the cover page of BMR. | |
| 2 | Check that the wash water analysis reports (if required) is attached to BMR. | |
| 3 | Check METIS generated fresh batch confirmed IMO (Issue Material Order) and deviated IMO attached with the BMR. | |
| 4 | Check the Raw Material issue coupons for completeness e.g. A.R. No., Batch No., Qty. dispensed against IMO and BMR and checked by sign and are attached with BMR. | |
| 5 | Check that the environmental conditions (temperature & RH) are within the limit as per BMR. | |
| 6 | Check line clearance checklist and cleaned/ partially cleaned card at each and every stage attached with the BMR. | |
| 7 | Check that the procedure, process parameter & equipment /Accessories is followed as per BMR and recorded properly. | |
| 8 | Check that all in-process records is attached to the BMR. | |
| 9 | Any planned or unplanned deviation like Change Control/Event in the process is properly documented and authorized (Refer CC No /Event No) and their photocopy attached to the BMR. | |
| 10 | Check the status of Shop Floor Observation. | Closed/Not closed |
| 11 | Check that the batch yield calculation and batch reconciliation are within the limit as per BMR. | |
| 12 | Check that all entries have done properly with sign and date and approved chemist has signed. | |
| 13 | Ensure that the batch is released by QA for further processing and the AQL sheet shall be attached to BMR. | |
| 14 | Check finished /micro/ validation sample/hold time has been withdrawn and its quantity documented properly and test requisition cum report attached with the BMR. | |
| 15 | All the observation listed in executed batch record review sheet is corrected by Production officer. | |
| 16 | Check the BMR history sheet comment. | |
| 17 | Check all the page number sequence in the executed BMR. |
- NOTE :
- Check Legible, Complete Set of BMR & Correctness Of entries (all stages) and then sign in BMR.
- Put tick mark (√) at Stage (At which stage BMR to be reviewed) and at the status of Shop floor Observation mentioned above.
- Annexure 4: Checklist for Filled BPR Review.
| Sr. No. | Checkpoints | Complies/Not Complies/NA |
| 1 | Check that all entries are filled at the cover page of BPR. | |
| 2 | Check that the BPR is authorized for Packing. | |
| 3 | Check that the METIS generated confirmed IMO (Issue Material Order) and the deviated IMO attached to the BMR. | |
| 4 | Check that the environmental conditions (temperature & RH) are within the limit as per BMR. | |
| 5 | Check line clearance checklist and cleaned/ partially cleaned card at each and every stage and attached with the BPR. | |
| 6 | Check packing material issue order against batch packing record. | |
| 7 | Check that printed and plain overprinted packing material specimen is attached and checked by the concerned packing officer and verified by QA. | |
| 8 | Check that the pack profile complies as per BPR. | |
| 9 | Check that the distribution of batch size matches with standard batch size. | |
| 10 | Check that the procedure, process parameter & equipment /Accessories are followed as per BPR and recorded properly. | |
| 11 | Check that the all in process records are attached to the BPR. | |
| 12 | Any planned or unplanned deviation like Change Control/Event in the process is properly documented and authorized (Refer CC No /Event No) and their photocopy attached with the BPR. | |
| 13 | Check that the primary packing material, secondary packing material and batch reconciliation are within limit as per BPR. | |
| 14 | Check that the Hold time/validation/ control sample / micro / stability samples are withdrawn and its quantity documented properly and test requisition cum report attached with the BPR. | |
| 15 | Check that the material return note for excess printed packing material is attached with the BPR. | |
| 16 | Check that the destruction of stereos & non- recoverable recovery is documented properly. | |
| 17 | Check that the Final Inspection Report and COA are attached with BPR. | |
| 18 | Check the quantity to be dispatched against the Material Transfer Note and its quantity documented properly in the BPR. | |
| 19 | Ensure that the Approved Packing Head/ Production Head have signed. | |
| 20 | Check status of Shop Floor Observation. | Closed/Not closed |
| 21 | All the observation listed in executed Batch Record Review Sheet is corrected by Production officer/ Packing Officer. | |
| 22 | Check BPR history sheet comment. | |
| 23 | Check all the page number sequence in the executed BPR. |
- Note:
- Check Legible, Complete Set of BPR & Correctness Of entries (all stages) and then sign in BPR.
- Annexure 5: Executed Batch Record Review Sheet.
Put tick (√ ) wherever it is applicable: (BMR/BPR)
Product: Batch No:
| Sr. No. | Page No. | Observation | Stage | Corrected By Production | Checked By QA |