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Placebo Medicine Batch – Procedure for Handling

A placebo batch of a product is processed as per regular formulation of that product except for the active ingredient or A dosage form that is identical to the drug product except that the drug substance is absent or replaced by an inert ingredient or a mixture of the drug product excipients quantitatively equivalent to those found in the drug product dosage form

Handling of Placebo Medicine Batch

1.0   PURPOSE:

    • The purpose of this SOP is to provide a procedure for manufacturing and packing of placebo batch and control to be followed for placebo batch.

2.0   SCOPE:

    • This procedure is applicable to all placebo batches at pharmaceuticals drug manufacturing plants.

3.0   REFERENCES:

    • In House

4.0   RESPONSIBILITY:

    • Quality Control department shall be responsible for –

    • Providing the required quantity of placebo for analysis purposes.
    • Intimate production for the manufacturing of batch for analytical purposes.
    • Provide the required quantity of batches based on the average weight of the tablet to production so that BOM shall be prepared by production.

    • The formulation development team shall be responsible for-

    • Providing approved PMD.
    • To approve the MBMR and MBPR whenever a batch is manufactured based on R &D requirements.

    • The production department shall be responsible for-

    • Providing the required quantity of placebo for other requirements.
    • Preparation of new BMR and generate BMR requests with batch details.
    • To receive the issued BMR and fill in the details of the operation.
    • To handle the BMR safely and return to QA after completion of the batch.
    • Raise the request for re-issuance of BMR and filling the data as per the old copy.
    • Generate the BOM in metis & take the Material against BOM.
    • To raise the intimation cum request form.

    • Quality Assurance shall be responsible-

    • To evaluate the “approval of manufacturing of placebo batch as per request”
    • Review the BMR and ensure safe destruction of residue, recovery, and manufacturing rejects of placebo batch.
    • Certify the Material return memo.

5.0   PROCEDURE – HANDLING PLACEBO BATCH:

    • Placebo batch shall be manufactured based on the requirement from:
      • Medical service department for clinical trials.
      • Quality control department.
      • Production /packaging department for new equipment /Machine change part trial/ new pack size.
      • FDD /Formulation development/Improvements/ADL.
      • For qualification of equipment.
      • Marketing department for demonstration purpose.
      • As per customer requirement.
      • For transportation trial.

Note: This is not a comprehensive list by itself. There may be other requirements that need to be approved by Head quality.

  • Approval/Authorization of Placebo batch:

    • As per the requirement an “Approval for manufacturing of placebo batch” shall be raised by the production department.
    • The concerned department shall raise a requisition for the batch as per the change control procedure.
    • Approval for manufacturing of batch shall be evaluated by the Quality Assurance Department, approved by Head Quality.
    • After receipt of the approval, Production Department shall prepare a soft copy of the new BMR and all concerned departments shall review it.
    • Necessary corrections shall be made in hard copy as well as soft copy and a hard copy shall be sent to QA as a draft.
    • QA shall check and review the draft BMR of placebo and make necessary corrections in draft copy (if required) and return to the production department for correction.
    • After correction production department shall send a soft as well as a draft copy of BMR to QA.
    • After finalization of BMR, it shall be saved in the protected drive-by QA.

    • The batch Numbering system for batch as per SOP Batch Numbering of System.

    • Prepare Work Order of the required consumable item (Raw materials) and raise Material requisition order as per the standard bill of material.
    • The batch record shall be requested by the user department as per the Document Request Form.
    • A separate page of BMR Issuance and Closing Register shall be maintained.

  • Procedure for manufacturing of Placebo batch:

    • A placebo batch can be manufactured based on the requirements of the stockholder (If need).
    • Production shall check the feasibility of equipment for placebo manufacturing.
    • Concerned Department shall intimate to production department for batch based on the average weight of tablets so that number of tablets can be accountable to prepare the BOM.
    • The production department shall raise approval for the manufacturing of the batch as per the change control procedure.
    • Approval for manufacturing of batch shall be evaluated by QA, approved by Head QA.
    • After receipt of the approval, Production Department shall prepare a soft copy of the new BMR and review by all concerned department and make necessary correction in hard copy as well as a soft copy after review and send the hard copy to QA as a draft,
    • Whenever other process parameters are to be required, the same shall be incorporated in BMR.
    • QA shall check and review the draft BMR of placebo and make necessary correction in draft copy and return to production department for correction, correction production sends soft as well as a draft copy of BMR to QA.

    • After finalization of BMR is save in protected drive-by QA.

    • Product name, batch number, Batch size, and manufacturing date shall be written in the batch manufacturing record.
    • The production officer shall write the general item code shall be given to the batch with the name of the ingredients required along with the pharmacopoeial grade, quantity, and unit of measurement in the manufacturing record of the placebo for analytical purposes.
    • The item code of the materials used for the placebo preparation shall be the same to all the respective product BMR and quantity should be proportionate to the respective product BMR.
    • The above details shall be verified by QA before issue.
    • After authorization of the BMR, the dispensing of excipients shall be done as per the dispensing SOP.
    • The Batch should be manufactured as per the instructions given in the BMR.
    • Raw materials required for the batch should be dispensed as per the work order.
    • Mix the ingredients in the same sequence as given in the respective Product BMR. Use a suitable SS container or polybag for the same. In the case of the product, the formulation follows the sequence of manufacturing as given in the respective BMR.
    • Each stage of manufacturing should be checked for reconciliation and in-process checks and recorded in the BMR by the production officer.

    • The stage up to which the placebo to be manufactured should be decided as per the requirement.

    • After completion of batch manufacturing, the bulk finished placebo should be packed as per the requirement. The bulk should be labeled as “ Bulk Finished placebo” and stored under lock and key.
    • The residual recovery and manufacturing rejects of the batch should be destroyed by the production officer under the supervision of quality assurance and EHS officer.
    • The production officer should hand over the batch for the intended purpose to the concerned departments such as ADL, Quality control, R&D, and packing.
    • The batch after completion of the intended purpose should be reconciled and destroyed by taking approval.
    • In case of placebo manufactured for FAT /Trial at party level or as per any other requirement, the same should be sent out of the premises by routine through warehouse as per point no2.
    • Label the placebo with the appropriate label.
    • Send the labeled placebo to the respective section Quality Control e.g. Finished good testing section, method development section, etc.
    • Quality control shall maintain a usage log of placebo and the remaining (excess) quality, if any, of placebo at the unit level. Placebo shall be destroyed by quality control.

  • Packing of placebo batch :

    • After completion of batch manufacturing, “requisition cum test report” should be raised and sent to the Quality control department for sampling /analysis of bulk placebo with details of tests required to be performed.
    • After the batch is released by Quality Assurance, the production person should issue the batch to Packaging Department.
    • A placebo Master Batch Packing Record should be compiled by Production Department, Approved By Quality Assurance, and authorized by the Head quality and batch packing can be executed based on approved master.
    • All overprinted or plain packaging material specimens of the batch should be as per location SOP.
    • All in-process checks during packing activity should be recorded in the batch packing record by the packing person.
    • After the batch packing is completed, the excess material if any should be sent to Warehouse through EMRM as per the SOP or destroyed after the certification of QA.
    • On-line packing rejects, machine rejects, residual recovery of the batch should be destroyed as per the SOP.
    • After the batch is released by QA, the packing department should deliver the batch to BSR.

  • Procedure for manufacturing of Placebo batch for analytical Purpose:

    • A placebo batch can be manufactured based on the requirements of Quality control other stockholders (If need).
    • Quality control should raise a request for a placebo batch.
    • QC/User shall intimate to Formulation development team/MSTG for requiring PMD for placebo manufacturing.
    • The formulation development team/MSTG shall provide PMD to site production for preparing a small quantity batch.
    • Production shall check the feasibility of equipment and raise the change control for manufacturing of placebo.
    • On receipt of the request from Quality control, the production department should raise approval for the manufacturing of the batch.

    • Approval for manufacturing of placebo batch should be evaluated by QA, approved by Head QA.

    • Production shall initiate the preparation of the respective document (e.g. BMR) and shall prepare the placebo by mixing the ingredients in the same sequence as per given the respective product BMR.
    • After receipt of approval production should take a photocopy of the manufacturing record or placebo for analytical purposes.
    • Product name, batch number, Batch size, and manufacturing date should be written in the batch manufacturing record.
    • The production officer should write the item code, name of the ingredients required along with the pharmacopoeial grade, quantity, and unit of measurement in the manufacturing record of the placebo for analytical purposes.
    • The item code of the materials used for the placebo preparation should be the same as per the respective product MBMR and the quantity should be proportionate to the respective product MBMR.

    • The above details should be verified by QA before issue.

    • After authorization of the BMR, the dispensing of excipients should be done as per the dispensing SOP.
    • In the case of solid dosage forms, mix the ingredients in the same sequence as given in the respective Product MBMR.Use a suitable SS container or polybag for the same. In the case of the product, the formulation follows the sequence of manufacturing as given in the respective MBMR.
    • Label the placebo with the appropriate label. (Refer Attachment-2)
    • Send the labeled placebo to the respective section of Quality control.
    • Quality control should maintain the usage log of placebo and the remaining (excess) quality, if any, of placebo at the unit level. A placebo should be destroyed by quality control.

NOTE: A validity of the placebo batch should be the same as the respective product shelf life. Placebo for stability shall be retained up to the last interval of stability. The same general item code shall be used for all placebo batches (Dummy) but in case the first item code is not closed, do not raise the other placebo batch.

6.0   ABBREVIATIONS:

    • ADL: Analytical Development Laboratory
    • BMR: Batch Manufacturing Record
    • BOM: Bill of Material         
    • BSR: Bounded Store Room
    • CCR: Change Control Record
    • EMRM: Excess Material Return Memo
    • FAT: Factory Acceptance Test
    • FDD: Formulation Development Department
    • IT: Information Technology
    • R & D : Research & Development
    • MBMR: Master Batch Manufacturing Record
    • MBPR: Master Batch Packing Record
    • MSTG: Manufacture Science of Technical Group
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pharmabeginers

Janki Singh is experienced in Pharmaceuticals, author and founder of Pharma Beginners, an ultimate pharmaceutical blogging platform. Email: [email protected]

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