SOP on the execution of exhibit batches
Objective
To lay down a procedure for the execution of exhibit batches.
Scope
This SOP is applicable for the execution of exhibit batches to the formulation plant of a Pharmaceutical company.
Responsibility
Officer/above of the production and quality assurance department shall be responsible.
Accountability
The Head of the Department shall be accountable for compliance and implementation of SOP.
Procedure
Raw material and packing material shall be received from the approved vendor and the warehouse person shall verify the material with the purchase order and Chelan/invoice. Qualification status shall also be checked for an approved vendor. The receipt of material shall be recorded.
The quality assurance department shall receive and review the technical transfer document as per SOP.
The quality assurance department shall prepare the Test Batch Monitoring Plan Protocol and if required then prepared the Hold Time Study protocol.
Raw material and packing material shall be received from the approved vendor and the warehouse person shall verify the material with the purchase order and Chelan/invoice. Qualification status shall also be checked for an approved vendor. The receipt of material shall be recorded.
On the basis of the TTD document production department shall prepare the batch manufacturing record and batch packaging record. The BMR and BPR shall review and approve by the quality assurance department.
On the basis of the TTD document Quality Control department prepared specifications, standard test procedures, and other QC-related documents required.
Preparation of BMR:
Each BMR shall have the following contents:
The header shall be repeated on each page of BMR and shall bear Master BMR No., effective date, MFC No., supersedes, product code, 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 a date for the template of the header and footer). The header of first page has some additional information that may not require in the header of pages 2 and onwards
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: The 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: The 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.
Manufacturing Date: The month and Year in which the dispensing of the batch has started, e.g. 09/2023 shall be assigned as the manufacturing date on the BMR.
Expiry Date: If the shelf life of the product is pre-defined then the detail will be Month and Year when the shelf life of the packed product finishes e.g. 09/2025 shall be assigned as the expiry date in the BMR. If the shelf life of the product is not defined and has a status to be established then there is no need to provide a column for the Expiry date.
Generic Name (if any): Basic / Pharmacopoeial name of the product shall be mentioned, on the BMR.
Strength / Composition: The quantity of each product unit dosage form shall be mentioned on the BMR.
MFC Number: Reference to the Master Formula Card shall be mentioned on the BMR.
Dosage Form: The dosage form of the product for e.g. Tablets / Injectables etc, shall be mentioned on the BMR.
The first page also has brief detail of the content of BMR and their a respective page number
The next page of the BMR shall include general instructions.
The next page of the BMR shall include a calculation sheet for the quantity of the API to be used in a batch, depending upon the potency of the Raw Material
Bill of Material: It shall include the name & quantity of each raw material, the unit of measurement, Item Code number, the A.R. Number, and the Expiry of all the ingredients. These details shall be mentioned in the BMR.
The following pages of BMR shall record various activities in sequential order, e.g. Dispensing, Sifting, Mixing, Granulation, compression, coating, etc in the case of tablets. BMR shall record various activities in a sequential order, e.g. Dispensing, Sifting, Mixing, Granulation, filling, etc in case of Oral suspension and capsules. BMR shall record various activities in sequential order, e.g. Dispensing, washing, sterilization, filling, sealing, etc in case of dry powder injection.
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 the manual recording of time and quantities used along with the doer & checker signatures, against each processing instruction.
Each critical control parameter shall have the doer and checker signature with the 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 to relevant SOPs shall be made wherever necessary.
In process/process parameters (along with the 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 online rejections (if any).
The last sheet in the BMR shall be the “Deviation Approval Sheet”.
Each BMR shall be checked & reviewed by the production in-charge and handed over to QA, after the 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 the Batch Packing Record shall contain the following information:
Header and footer, except that the title shall change to “Batch Packing Record”.
The footer shall be as.
Product Name: The brand name of the product shall be mentioned on the BPR.
Batch Number: As per Batch numbering 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.
Shelf Life: The shelf life of the product shall be mentioned.
Batch Size: As per requirements
Packing Started On: The batch packing starting date shall be mentioned on the BPR.
Packing Completed On: The date of completion of the packing operation of the batch shall be mentioned on the BPR.
Manufacturing Date: As per SOP.
Expiry Date: As per SOP.
Packing Configuration: The number of counts per unit primary pack will be defined in this column.
Dosage Form: As per Requirement.
The first page also has brief detail of the content of BPR and their respective page number.
The next page of the BPR shall include general instruction
Bill of Material: It shall include material code, the name & quantity of each packaging material, a unit of measurement, the 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.
Hereafter shall be followed.
After the completion of the packing activity, the packing yield shall be reconciled.
Each BPR shall have the “Batch Packing Record Review Sheet” and “Deviation Approval Sheet” at the end of the batch, respectively.
Review of BMR / BPR by Production:
Before the commencement of BMR/BPR preparation, the Production officer/executive shall get the “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 the following methodology:
The BRPF number shall be of twelve (12) alphanumeric characters for eg. “BRPF/10-0001”. 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 characters shall represent the year of manufacturing i.e.”23” for the year 2023.
The 8th characters represent a dash”-“.
The 9th, 10th, 11th & 12th characters (0001) represent the sequential serial numbers of the BRPF.
After the preparation of BMR/BPR, the Production officer/Executive shall attach BRPF with a draft of the Master BMR / BPR, and forward it to the 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 the 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 numbers 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: The numbering system shall consist of Eleventh (11) alphanumerical characters.
For example, for the first version of BMR for “ tablets, “MRE/TAB/01-00” shall be assigned.
The 1st & 2nd characters ‘MR’ shall denote “Manufacturing Record”.
The 3rd character ‘E’ denotes ‘Export’ for the export market.
The 4th character represents a forward slash i.e.”/”. The 5th, 6th, 7th characters ‘TAB’ shall represent the product code.
The 8th character is again a forward slash i.e.”/”. The 9th& 10th characters “01” represent the batch size of the product. The 11th 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 “MRE/TAB/01-01”, 02 ……..10 respectively.
Master BPR: The numbering system shall consist of thirteen (13) alphanumerical characters.
For example, for the first version of BPR for “Tablets”, “PRE/TAB/00” shall be assigned.
In the master BPR number “PRE/TAB/00”, the first two characters ‘PR’ shall denote “Packing Record”.
The 3rd character ‘E’ denotes ‘Export’ for BPR (s) for the export market (e.g. PRE/TAB/00)
The 4th character is a forward slash ”/”.
The 5th, 6th, and 7th characters ‘TAB’ shall represent the product code as per SOP on Batch numbering of Drug Products.. The 9th character ‘U’ represents the pharmacopoeial grade of the API used. ‘U’ shall be replaced by “E” for Ph. Eur. for BPR (s) for the export market
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.
The execution of the batch shall be done as per the batch manufacturing record.
Approval, control, and issuance of BMR / BPR shall be done as per SOP.
All the in-process parameters should be within the specified limit and shall be recorded accurately and properly in BMR and BPRs.
In-process parameters shall be checked both by the production person and the IPQA person in a specified time.
At the end of each process, the sample shall be sent to the QC dept. for testing. The next process shall be started after receiving the release from QC.
The biostudy, stability study, QC, and retention samples shall be collected as per SOP.
The exhibit batch shall be stored in Finished good quarantine as per SOP.
The BMR and BPR shall be checked by the production dept. and IPQA. After review of IPQA, the BMR/BPR copy shall be sent to the QA dept. (Documentation) for further review. QA dept. shall review the document put them in a lock and key. The BMR/BPR shall be stored after 1 year of the expiry date or after 5 years from the manufacturing date whichever is later.
List of Annexures / Formats
Not Applicable
References (if any)
SOP on SOP
SOP on preparation, issue, control, and revision of BMR and BPR.
Reason for Revision
New SOP
Abbreviation and Definitions.
SOP: Standard Operating Procedure
BMR: Batch Manufacturing Record
BPR: Batch Packaging Record
Eur. : European Pharmacopoeia
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