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SOP on preparation, control, issuance and revision of Batch Manufacturing and Batch Packing Records

SOP on preparation, control, issuance and revision of Batch Manufacturing and Batch Packing Records

  • Scope: This procedure is applicable to the manufacturing & packing records being generated at the formulation Plant of Pharmaceutical company.
  • Responsibility:
    • Executive Production – Preparation of BMR / BPR.
    • Head Production / nominee – Checking / Review of BMR / BPR.
    • Executive QA – Review of BMR / BPR / Issuance of BMR / BPR code Number.
    • Head-QA / nominee – Approval of BMR / BPR.
  • Accountability:  Head – QA / Head – Production / Plant Head shall be accountable for the compliance of this SOP.
  • Procedure:
    • Each batch of the product shall be manufactured by following written manufacturing procedures in the form of BMR and packed by following written packing procedures in the form of a BPR, which shall be uniquely numbered.
    • BMR shall refer to the Batch Manufacturing Record, which shall include the processing operation of dispensing, sifting, mixing, granulation, compression, coating, capsule filling, dry powder filling, vial washing, tunnel sterilization, filling and sealing.
    • BPR shall refer to Batch Packing Record, which shall include the primary packing as well as secondary packing operations in case of unit dosage form like tablets & capsules. And, primary packing material is incorporated in BMR in case of dosage forms like Injection & Dry Syrup.
    • Batch Manufacturing Record (BMR) and Batch Packing Record (BPR) shall be prepared based on the Master Formula Card and Master Packing Record.
    • For the new products, the BMR / BPR shall be prepared based on the Master formula card provided by   R & D.
  • Preparation of BMR:
    • Each BMR shall have the following contents:
    • The header shall be repeated on each page of BMR and shall bear the product name, batch number and sequential page number along with the title “Batch Manufacturing Record”. The header shall also have a designated space for putting a stamp of “Master Copy” and “Controlled Copy” duly signed with date.
    • The footer shall also be repeated on each page of the BMR, but the name of the signatories shall be handwritten on the first page only.
    • The first page of BMR shall contain the following information:
      • Product Name: Brand name of the product shall be mentioned on the BMR.
      • Batch Number: A unique batch number shall be mentioned on the BMR, for each batch of a particular product, as per “SOP on Batch Numbering of drug products”.
      • Master BMR Number: Master BMR Number shall be assigned by QA, which shall consist of a unique document control number, issued to each BMR.
      • Shelf Life: Shelf life of the product shall be mentioned.
      • Batch Size: Maximum number of dosage form units, which can be manufactured in a batch, shall be mentioned in the BMR in case of Tablets, Capsules & Oral Suspension.
      • Batch Started On: The batch starting date shall be mentioned on the BMR, which shall be based on the date of dispensing of raw materials.
      • Batch Completed On: Date of completion of manufacturing operation of the batch shall be mentioned on the BMR.
      • Manufacturing Date: Month and Year in which the dispensing of the batch has started, e.g. DEC. 2017, shall be assigned as the manufacturing date on the BMR.
      • Expiry Date: Month and Year, when the shelf life of the packed product finishes g. NOV. 2017, shall be assigned as the expiry date in the BMR.
      • Generic Name (if any): Basic / Pharmacopoeial name of product shall be mentioned, on the BMR.
      • Strength / Composition: Quantity of each product unit dosage form shall be mentioned on the BMR.
      • Reference Number: Reference to the Master Formula Card or the BMR of the loan licensee location shall be mentioned on the BMR, in case of Tablets & Capsules.
      • Dosage Form: Dosage form of the product for e.g. Tablets / Capsules / Dry syrup / Injectables etc, shall be mentioned on the BMR.
      • Bill of Material: It shall include the name & quantity of each raw material, unit of measurement, Item Code number, A.R. Number, Expiry / Retest date of all the ingredients. These details shall be mentioned in the BMR.
    • Next page of the BMR shall include a calculation sheet for quantity of the API to be used in a batch, depending upon the potency of the Raw Material.
    • The following pages of BMR shall record various activities in a sequential order, e.g. Dispensing, Sifting, Mixing, Granulation, compression, coating etc in case of tablets.
    • Each stage of manufacturing shall have a separate line clearance sheet, as a part of BMR.
    • Each processing operation shall be written in the form of specific instructions, in a tabular form. Adequate space shall be provided for manual recording of time and quantities used along with the doer & checker signatures, against each processing instruction.
    • The critical processing steps or Critical control parameters shall be identified / highlighted in the BMR using a bell “%” sign. Each of these critical processing steps shall have a standard time / temperature etc mentioned in the BMR.
    • Each critical control parameter shall have the doer and checker signature with date.
    • Against each operation number, the operator shall put his / her initials. Therefore, appropriate space shall be provided for the signatures, against each operation.
    • “Precautions / cautions / note” shall be typed in ‘bold’ in the remarks column, if required.
    • The reference of relevant SOPs shall be made wherever necessary.
    • In process / process parameters (along with acceptance limit), shall be clearly mentioned in the BMR.
    • Preferably, each stage shall have a standard yield specification.
    • At the end of the manufacturing activity, batch yield reconciliation shall be done, along with on line rejections (if any).
    • The last sheet in the BMR shall be “Deviation Approval Sheet”.
    • Each BMR shall be checked & reviewed by production in-charge and handed over to QA, after completion of the batch manufacturing activities.
    • Each BMR shall have a ‘Batch Review Check List’, where all manufacturing activities shall be reviewed and signed off by QA.
  • Preparation of BPR:
    • Each BPR shall have the following contents:
    • The first page of Batch Packing Record shall contain the following information:
    • The header shall be as per above, except that the title shall change to “Batch Packing Record”.
    • The footer shall be as per above.
      • Product Name: Brand name of the product shall be mentioned on the BPR.
      • Batch Number: As per SOP
      • Master BPR Number: Master BPR Number shall be assigned by QA, which shall consist of a unique document control number, issued to each BPR, as per clause number 10.
      • Shelf Life: Shelf life of the product shall be mentioned.
      • Batch Size: As per Requirement.
      • Packing Started On: The batch packing starting date shall be mentioned on the BPR.
      • Packing Completed On: Date of completion of packing operation of the batch shall be mentioned on the BPR.
      • Manufacturing Date: As per SOP
      • Expiry Date: As per SOP.
      • Packing Configuration: Pattern / fashion in which strip / blister / bottles, primary and secondary packing (orientation) is carried out, e.g. 10 x 10 x 60 for 10 tablets in a strip / blister (primary pack), 10 strips / blister in a carton (secondary pack) and 60 cartons in a shipper (secondary pack).
      • Dosage Form: As per Requirement.
      • Input Batch Number: The input batch number (BMR) from which the batch allocation has been done shall be mentioned .
      • Bill of Material: It shall include material code, the name & quantity of each packaging material, unit of measurement, required qty of each Packing material & A.R. Number. These details shall be mentioned in the BPR.
    • Each stage in the process of packing i.e. primary packing and secondary packing shall have a separate line clearance sheet.
    • The impression of all the stereos to be used for overprinting shall be taken on the BPR, therefore, appropriate space shall be provided for the same.
    • The stereo impression shall be checked by production and verified by IPQA.
    • After the completion of the packing activity, packing yield shall be reconciled.
    • Each BPR shall have “Batch Packing Record Review Sheet” and “Deviation Approval Sheet” at the end of the batch, respectively.
  • Review of BMR / BPR by Production:
    • Before commencement of BMR/BPR preparation, Production officer/executive shall get “Batch Record Preparation Format” (BRPF) which shall be issued by QA.
    • The Batch Record Preparation Format has a unique number. The number shall be assigned by QA by using following methodology:
    • The BRPF number shall be of twelve (12) alphanumeric characters for eg. “BRPF/17-0001”. The first four characters shall be the name of the format i.e. ‘BRPF’ followed by the 5th character a forward slash”/”.
    • The 6th & 7th character shall represent the year of manufacturing i.e.”17” for the year 2017.
    • The 8th characters represent a dash”-“.
    • The 9th, 10th, 11th & 12th character (0001) represent sequential serial number of the BRPF.
    • After the preparation of BMR/BPR, Production officer/Executive shall attach BRPF with a draft of the Master BMR / BPR, and forward it to production department head for review.
    • The production department head shall review the master batch record to verify the Critical process / control parameters, sequence of activities, instructions, cautions etc and put his comments on the BRPF .
    • If the production head is satisfied with the master batch record, the production head shall sign off the batch record, and send the draft BMR / BPR back to QA for review.
  • Review of BMR / BPR by Quality Assurance
    • After the review by production head, the batch document shall be forwarded to QA, along with the BRPF, for review and subsequent approval.
    • QA Executive shall assign a ‘Batch Record Preparation Form’ number to the BRPF.
    • A logbook of BRPF number shall be maintained by QA.
  • Numbering of Master BMR / BPR
    • Once QA Executive has received & reviewed the draft BMR / BPR, a unique master BMR / BPR number shall be assigned to each master batch record.
    • Master BMR numbering system (For Oral Dosage form): Numbering system shall consist of Twelve (12) alphanumerical characters.
      • For example, for the first version of BMR for “Tablets, “MR/TAB/01-00” shall be assigned.
      • The 1st & 2nd characters ‘MR’ shall denote “Manufacturing Record”.
      • The 3rd characters ‘D’ shall denote “Domestic”. ‘D’ shall be replaced by ‘E’ which shall denote ‘Export’ for BMR (s) for export market.
      • The 3th character represents a forward slash i.e.”/”. The 4th, 5th, 6th characters ‘TAB’ shall represent the product is Tablets.
      • The 7th character is again a forward slash i.e.”/”. The 8th& 9th characters “01” represents the batch size of the product. The 10th character is a dash “-“.
      • The last 2 characters, “00” shall denote the version number of the master BMR. Any revision in master BMR for e.g. change in process, batch size, equipment change and change in parameters shall be represented as ““MRD/CFDCI/01-01”, 02 ……..10 respectively..
    • Master BPR (For Oral formulations): Numbering system shall consist of twelve (12) alphanumerical characters.
      • For example, for the first version of BPR for “Tablets, “PRD/TAB/00” shall be assigned.
      • In the master BPR number “PRD/TAB/00”, the first two characters ‘PR’ shall denote “Packing Record”.
      • The 3rd character ‘D’ shall denote “Domestic”. ‘D’ shall be replaced by ‘E’ which shall denote ‘Export’ for BPR (s) for export market .
      • The 4th character is a forward slash ”/”.
      • The 5th, 6th & 7th characters ‘TAB’ shall represent the product code as per SOP on Batch numbering of Drug Products.
      • The 10th character is again a forward slash ”/”.
      • The 11th & 12th characters, “00” denotes the version number of the BPR. Any change in packing material dimensions, item code, sealing roller temperature, heating and forming plate temperature.
    • QA executive shall prepare & maintain a Master List of all the master BMR / BPR numbers.
    • This list of master BMR / BPR shall be updated as and when required.
  •             Approval of BMR / BPR
  • QA Executive/Officer first ensure the completion of ‘BRPF’ & then review all the aspects of the draft BMR / BPR. After reviewing the draft BMR / BPR the same shall put his comments on the BRPF, assign the Master BMR / BPR number and forward the same to Head QA, for review & approval.
  • Head QA shall review the draft of Master BMR / BPR, for cGMP and Regulatory  compliance and finally approve the Master BMR / BPR by signing off the batch record, after being satisfied with the same in all respects.
  • Once the batch record has been approved by Head-QA, Executive /Officer QA shall stamp the same as “Master Copy” with Sign & Date at a designated place on the header of each page.
  • Control of Master Copies of Batch Manufacturing and Batch Packing Records.
  •  The approved Master copy of BMR / BPR shall remain in QA custody.
  • A photocopy of the BMR / BPR shall be issued to production, for manufacturing of a new batch of particular product.
  • A list of all the master BMRs shall be maintained by QA .
  •  A list of all the master BPRs shall be maintained by QA .
  • After completion of the Batch manufacturing & packing, the production department shall  complete the batch records and submit the same to QA for batch release . The entries of the batch records shall be recorded in a log book .
  • Review & Storage of Filled Batch Manufacturing and Batch Packing Records
  • After receiving the completed batch records, QA Officer / Executive shall review the filled BMR / BPR and attach review checklist  along with the batch records. The reviewed batch records shall be forwarded to Manager QA for signing off the BMR / BPR for release / dispatch of a batch. After that, QA Executive shall put the filled BMR / BPR into a batch docket (envelop) along with all the line clearance sheet, tags, dispensing labels and QC test reports (COA).
  •  Retention period of Filled Batch records
  • The filled batch records for each product shall be kept in QA custody, under lock and key.
  • These batch records shall be retained (with QA) for a period of two (02) years from date of expiry of the product batch or 5 years from date of manufacturing of the batch, whichever is later
  • Whenever a batch record is required by anybody for reference / review, the same shall be issued, after an approval from Head QA. The entries of such batch records shall be recorded in a log book.
  • Destruction of Batch Manufacturing and Batch Packing Records
    • After completion of the retention period of the batch records, these batch records shall be destroyed by QA Executive, using a paper shredder.
    • A record of destruction shall be maintained in “BMR / BPR Obsolete / Destruction Record”.
  • Issuance & Retrieval of Batch Manufacturing and Batch Packing Records
    • The issuance of BMR / BPR, for manufacturing a new batch, shall be controlled by QA department.
    • The production department shall send a prior intimation to QA through ‘BMR / BPR Request Form’ for the purpose of issuance of BMRs / BPRs.
    • Incase division of batch at packing stage (Allocated Batch) of any dosage form i.e. Tablet, Capsule & Injection then the production department shall send a prior intimation to QA through ‘BMR / BPR Issuance Request Form  along with filled ‘Batch Packing Allocation form’ .
    • QA shall get the master copy of BMRs / BPRs photocopied, stamp it as “Controlled Copy” in a designated place on the header and put initials on the same along with the date.
    • QA Executive/Officer shall write the batch number, manufacturing and expiry date, on each BMR / BPR page, before issuance to production.
    • The record of issuance & retrieval of BMR / BPR shall be maintained in the “Logbook for issuance of BMR / BPR” .
    • If the plan to manufacture a batch is dropped, the blank BMR / BPR shall be returned to QA with “BMR/BPR return request form . The blank BMR / BPR shall be destroyed using a paper shredder.
    • Incase, additional pages of BMR / BPR are required by production for additional entry, the same shall be issued by putting the word “Additional Page”.
  • Revision of Master Batch Manufacturing / Batch Packing Records
    • The revision of a master BMR / BPR shall be carried out, by following Change Control procedure (refer SOP on Change Control Procedure.
    • The master copy of the superceded version shall be stamped as “obsolete” & record the same as per  and archived the Obsolete copy with QA, till 5 years (for reference purpose)

6.0       List of Annexure / Formats

  •  NA

7.0References

  • SOP on SOPs
  • SOP on change control procedure
  • SOP on release of finished product
  • SOP on batch numbering of drug products
  • SOP on document numbering and data control

7.0 Reason for Revision

  • New SOP

8/0 Abbreviation & definition:

BPR                –           Batch Packing Record

BMR                –           Batch Manufacturing Record

F R & D           –           Formulation Research & Development

BRPF              –           Batch Record Preparation Form                                            

 

 

 

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About Pharmaceutical Guidanace

Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field. During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube

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