of tolerance, an investigation into the non- ed.

[Company Logo] STANDARD OPERATING PROCEDURE

Doc. NumberPH47

Rev. [A]

DCO [12345]

Eff. Date[MM/DD/YY]

Page 5 of 11

Proprietary & ConfidentialInformation

PRODUCT RELEASE

7.2 Quality Assurance performs a review of the batch production record. The following items are checked as part of the batch record review procedure:

7.2.1 The master batch record is approved by Quality Assurance.

7.2.2 The master batch record and procedures are current at the time of operation, e.g. the batch record reflects the current effective revision of the Master Batch Record.

7.2.3 All pages are present in the batch record and each page is identified with the correct lot numbers.

7.2.4 No superfluous documents are included in the batch record. For example, identical duplicate copies of memos, batch records, and documents unrelated to the production of the batch, etc.

7.2.5 All required entries are completed with the appropriate data and all data meets required target range.

7.2.6 An explanation is present detailing the reason for issuance of replacement pages.

7.2.7 All quality issues observed in the batch record are resolved and formally documented.

7.2.8 All additional comments or entries in the documents are appropriate and do not impact the quality of the product.

7.2.9 Any hand written comments are well justified and initialed/dated.

7.2.10 All cross-outs are initialed and dated, with a brief comment explaining the reason for the cross out, or in accordance with internal document completion procedures.

7.2.11 All spaces must contain the information or “N/A”. If there are blank spaces, indicate that information was not recorded at the time of review.

7.2.12 All calculations have been performed correctly. Spot check calculations for theoretical, actual yield, weights, etc.

7.2.13 All accountability/reconciliation calculations are present and are within the allowed tolerance, and all entries and calculations were performed correctly. If results are outsideconformance must be complet

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BATCH RECORD REVIEW SOP 1.0 PURPOSE :To define the salient points to be checked by QA during batch record review.2.0 SCOPE :To assign, individual responsibilities to QA and Production with regard to proper entries and completion of batch records in time to ensure batch product release.3.0 RESPONSIBILITY :Q.A.Manager, Production manager, Q.C. Manager3.1 The responsibility to ensure batch records are completed and forwarded to QA for review is with Production.3.2 The responsibility to ensure review of batch records and release of batch Product is with Quality Assurance.4.0 PROCEDURE :4.1 General Checks4.1.1 Records are error free, tidy, legible and accurate.4.1.2 Good quality of photocopy.4.1.3 The timings of each process is sequential with procedure in BMR.4.1.4 Any overwriting/cancellation of entry should be signed by responsible officer.4.1.5 Any deviation in process should be mentioned in batch summary sheet. QA to ascertain impacton product quality at the time of review before product release.4.2 Work order4.2.1 Duly authorised & signed.4.2.2 Item code/AR Nos filled against each item.4.2.3 Correct calculation of gross/tare/net.weight4.2.4 Reconcile any excess issues/returns in work order4.2.5 Ensure each item issued has two signatures of weighed by & checked by.4.2.6 Ensure batch material issue/receipt, signature of responsible officers.4.3 BMR / BPR checks4.3.1 Cleanliness record is entered for both equipment and areas.4.3.1.1 Equipment code numbers4.3.1.2 Previous product details4.3.1.3 Cleanliness checked by signature4.3.2 Line clearance certification for all operations signature of Q.A4.3.3 Operation timings and name of operators are entered.4.3.4 Ensure critical operations are counter checked by second person.4.3.5 Verify proper timings of in - process control.4.3.6 Input/Output materials reconciliation Vield of final product at each stage is within limits.4.3.7 Check for proper QC reports.Eg: T.I.S. T.R.F. PRRF are attached to BMR/BPR4.3.8 Check over printed details of printed specimen against notation in BPR.4.3.9 Check batch summary sheet for deviation recording and authorisation.4.4 BPR4.4.1 Work Order sheet : Qty Std. / Qty issued / Checked byEnsure the individual key material qtyAR Nos. of all packing materials.4.4.2 Packing operation sheet4.4.2.1 Inprocess checks are done as per frequency mentioned in BPR.4.4.2.2 Printed packaging materials details as per BPR.4.4.2.3 Materials usage reconciliation data4.4.2.4 Hence clearance in packing / overprinting4.4.2.5 Final Yield analysis4.4.2.6 Sequence timings should be checked4.4.3 PRRF to be checked with QC reportNote: The complete batch record after review and corrections will be approved by quality assurance. These records will be in safe custody of quality assurance.

BATCH RECORD AUDIT - SOP OBJECTIVE:

To establish procedure to be followed while auditing the batch production, Batch Packing Records and analytical records

RESPONSIBILITIES:

Manager Quality Assurance / Manager Quality Control and Assurance shall be responsible for carrying out batch records audit as a part of batch - release.

PROCEDURE:

1. All the production records including those for packing and labeling and analytical records shall be audited by Quality Assurance to determine compliance with all established approved and written procedures before a batch is released for distribution. Any discrepancy or failure of a batch or any of its components to meet any of its specifications shall be thoroughly investigated.

2. Any handwritten change to the equipment’s, materials, weights, procedures and process parameters shall be signed and dated by the Asst. Production Manager / Production Manager / Production Incharge and accompanied by justification and approved by Quality Assurance Manager / Change Control Committee.

3. A written record of investigation shall be made and shall include the conclusion and follow-up. Following parameters shall serve as guidelines while carrying out appropriate review of batch records.

4. Batch Manufacturing Records (BMR):

Manager Quality Assurance / Quality Assurance Inspector shall review and check the following records for their correctness and compliance:

4.1. Issue of batch Manufacturing records formats by Quality Assurance with signature and date of issue.

4.2. Batch Manufacturing records issued are appropriate and in accordance with the current and approved Master copy of BMR.

4.3. Each significant step in the manufacturing, processing is accomplished including dates and identity of major equipments and lines used.

4.4. Specific identification of each batch of in-process material.

4.5. Components used during the processing or manufacturing are weighed correctly and weighing operation witnessed by the other person.

4.6. In process Quality Control checks and results.

4.7. Process control checks and results.

4.8. Calculations of yields at appropriate phases of manufacturing or processing and the percentage of theoretical yield and limits established and indicated in BMR.

4.9. Each critical step in the manufacturing and processing is witnessed by the other person as indicated in batch Manufacturing records.

5. Batch Packing Records:

Manager Quality Assurance / Quality Assurance Inspector shall review and check the following records for their correctness and compliance:

5.1. Issue of batch packing records format by Quality Assurance with the signature and date of issue.

5.2. Batch packing records formats issued are appropriate and in accordance with the current and approved Master copy.

5.3. Inspection of the packing and labeling area before and after use.

5.4. Actual yield and percentage of theoretical yield at appropriate phases of operations as indicated in batch packing records.

5.5. Reconciliation’s records.

5.6. Specimens of all labeling used in packing and signed by packaging supervisor and Quality Assurance Inspector.

5.7. Description of product containers and closures used and their identification.

5.8. Identification of persons performing and supervising or checking each significant step in the operation.

5.9. Results of examinations made as per "Product Inspection" report.

5.10. Any investigation made there of.

6. Batch Analytical Records:

Manager Quality Assurance / Quality Assurance Inspector shall review and check the following records for their correctness and compliance:

6.1. All the analytical reports with protocols from relevant sections are enclosed.

6.2. All the analytical reports with protocols are duly signed by analyst and certified by Manager Quality Control with his opinion / remarks on the tests carried out.

6.3. All the supporting analytical documents are enclosed to the respective analytical reports.

6.4. Dates are entered at appropriate places with signatures.

6.5. Certificates of analysis is enclosed with remarks / opinion of Manager Quality Control and signature of analyst and Manager Quality Control.

7. General:

7.1. There shall be no white ink used for correction on any written matter.

7.2. The handwritten changes shall be made only after putting a cross line on the matter to be corrected and the signature of the person who made the changes and date.

7.3. All the entries shall be appropriately registered and shall be signed with date.

7.4. There shall be no overwriting on any of the entries in batch records.

7.5. Each component shall be added to the batch by one person and independently verified by a second person whose signature shall be recorded on the batch manufacturing record.

7.6. After auditing the batch manufacturing records including those for packing and labeling and analytical records, and inprocess samples Manager Quality Assurance shall release / reject the batch and sign with date on the batch records.

7.7. All the logbooks, raw data books shall be counter checked while auditing the batch records, and analytical records.

7.8. Investigation record shall be prepared if any unexplained discrepancies or the failure of a batch or any of its components to meet any of the specification with conclusion and follow up.

Issue, Entry, Review and Control of Batch Manufacturing Records

    Purpose   : To detail the procedure for issue, entry, review, release and control of Batch Manufacturing Records.

     Objective   :  To provide a documented procedure for issue, entry, review, release and control of Batch Manufacturing Records

by QA.

    Scope       : Applicable while issue, entry, review, release and control of Batch Manufacturing Records.

4.0      Responsibility  :

        Primary: Officer–QA / Officer–QC/ Officer-Production

        Secondary: Manager-QA/ Manager- QC/ Manager- Production   

5.0       Procedure :

          Issue of batch manufacturing record ( by Quality Assurance)

      Based on Production planning, production manager shall decide on the product and the number of batches to

be produced in the month.

      Production supervisor shall raise the requisition for the batches to be taken for the week and forward it to

Quality Assurance.

      On receipt of Batch Manufacturing Record issue requisition QA personnel will verify the details entered in the

requisition form.

      A photocopy of the MASTER COPY of the required Product Batch Manufacturing Record will be taken.

      All the pages of the photocopied sheet of Product Batch Manufacturing Record shall be signed and dated by

QA Personnel.

      Check for the correctness of the Batch number by verifying the BMR register.

      Enter the details of Date, Product, Batch No, Batch size, Manufacturing Date, Expiry Date and issued by details

in the BMR register.

      Check and allot expiry date by referring to master list of product shelf life.

      If there is a deviation for change in batch size or any other equipment / process change raise deviation

approval form as per deviation procedure SOP.

      Enter the Batch No. on all the pages of the BMR and get it authorized by QA Manager or in absence by QA

Executive or QA Officer.

      Insert the signed Batch record in a BMR cover and enter the details of product name, Batch Number, Batch

size. Manufacturing date and Expiry date.

      Batch record along with the Batch Record register shall be sent to production, the production person receiving

the batch record should sign on the batch record register to acknowledge the receipt of batch record.

      QA person who has issued Batch Record shall sign the “issued by” on batch record issue requisition sheet and

file the same for future reference.

          Entry of Batch Manufacturing Records (By Production Personnel)

      On receipt of BMR Production Manager / Dy. Production Manager shall check the BMR and sign on the first

page.

      The calculation sheet should be forwarded to stores for entry of the relevant AR Nos., quantity and assay

value.

      After the relevant entry store forward the sheet to production department where production chemist fill

equipment status detail where line clearance status and ECR No. should be entered for each equipment.

      Now operator fill the next form of process to be carried out for particular reactor in which starting and ending

time should be entered and finally sign by operator and checked by in-charge.

      After completion of every reaction in each of the particular reactor intermediate should be send to QC Lab. for

checking of completion of reaction, LOD etc.

       After final product obtained send the request to QC for complete analysis of the product and send the

analytical report.

      Fill all remaining entry and attach all analytical report.

      BMR should be then send to QA department for Review.

        Review and control of batch manufacturing record ( by Quality Assurance)

      Batch No. should be checked by Quality assurance department.

      Review the Analytical report of all raw materials attached with BMR and check the A.R. No.

      Review the Equipment Cleaning Record for each equipment and relevance of line clearance by QC.

      Review the deviation in process which is predefined.

      If any deviation present change deviation report of process should be there. Review the report of change in

deviation and its significance in the process.

      Check the quantity of solvent recovered in the process. Recovery should be proper and complete.

      Wet material packing record should be reviewed.

      Drying record as well as dry material packing record should be checked and reviewed.

      Check the Analytical report of finished product generated by Q C Department.

      Finally attach the review report with specific number given by QA department duly dated and singed by QA

manager. 

      If everything is fine then pass the batch and allow it for dispatch.

      Send this record in safe custody of Quality Assurance department.

      If anybody needs the copy of BMR it should be given as a control copy with permission of QA Manager.

      Every BMR should be saved for five years from manufacturing and after that it should be destroyed as per

SOP.

Batch Manufacturing Record Review     Purpose   :    To define the salient points to be checked by QA during batch record review.

     Objective:   To provide a documented procedure for points to be checked by QA during batch record review.

     Scope       : To assign individual responsibilities to QA and Production with regard to proper entries and completion of batch

records in time to ensure batch product release.

4.0      Responsibility  :

        Primary: Officer–QA / Officer–QC/ Officer-Production

        Secondary: Manager-QA/ Manager- QC/ Manager- Production   

5.0       Procedure :

          General Checks

      Records are error free, tidy, legible and accurate.

      Good quality of photocopy.

      The timings of each process is sequential with procedure in BMR.

      Any overwriting/cancellation of entry should be signed by responsible officer.

      Any deviation in process should be mentioned in batch summary sheet. QA to ascertain impact on product

quality at the time of review before product release.

          Work order

      Duly authorized & signed.

      Item code/AR No. filled against each item.

      Correct calculation of gross/tare/net weight.

      Reconcile any excess issues/returns in work order.

      Ensure each item issued has two signatures of weighed by & checked by.

      Ensure batch material issue/receipt, signature of responsible officers.

          BMR Checks

      Cleanliness record is entered for both equipment and areas.

      Equipment code numbers.

      Previous product details.

      Cleanliness checked by signature

      Line clearance certification for all operations signature of Q.A.

      Operation timings and name of operators are entered.

      Ensure critical operations are counter checked by second person.

      Verify proper timings of in - process control.

      Input/Output materials reconciliation Yield of final product at each stage is within limits.

      Check for proper QC reports.

      Check batch summary sheet for deviation recording and authorization.

          BMR

      Work Order sheet: Qty Std. / Qty issued / checked by Ensure the individual key material qty, AR Nos. of all

packing materials.

Note: The complete batch record after review and corrections will be approved by quality assurance. These

records will be in safe custody of quality assurance.

6.0      Reference Document :      Not applicable

7.0      Abbreviations :

        QA   = Quality Assurance department

        QC = Quality Control

        BMR = Batch Manufacturing Report

        AR No. = Analytical Report Number