Preparation, Approval, Review and Control of MFC and MPC for Manufacture of Pharmaceutical Products

Preparation, Approval, Review and Control of MFC and MPC for Manufacture of Pharmaceutical Products

Objective: To lay down a procedure for the Preparation, Approval, Review and Control of MFC for Manufacture of Pharmaceutical Products.

Scope:  This Standard Operating Procedure is applicable for preparation and implementation of MFR for all products manufactured at pharmaceutical formulations plants.

Campaign :Taken together in tandem/ continuously during the manufacturing of a product.

PM: Packaging Material.

RM: Raw Material.

R&D: Research and Development.

BPR : Batch Packing Record; filled / unfilled controlled copy of MPC along with other requisite forms/records, which reveals all the information of a batch of a product.

BMR : Batch Manufacturing Record; filled / unfilled controlled copy of MFC along with other requisite forms/records, which reveals all the information of a batch of a product.

Both MFC and MPC shall be prepared  with a provision of recordings, which shall be done during manufacture of a product by the competent Production and Quality staff.

MPC detailing Packaging procedure.

MFC detailing Manufacturing procedure and

Master Document of Manufacturing and Packing : Document, which reveals all approved instructions regarding manufacturing of the product starting from dispensing of raw materials, packaging materials, manufacturing  and packaging operations including in-process checks and final dispatch for distribution, to get an appropriate quality of finished product. This document shall comprise of two separate parts-

Abbreviations and Definitions:

Responsibility

Scientists, R&D and Process Development Scientist, Documentation Cell, shall be responsible for preparation, and review of manufacturing procedure of products.

Scientist, Packaging Development shall be responsible for preparation of the MPC for packaging procedure and  Packaging Development shall be responsible for review of the MPC.

Head-R&D shall be responsible for approving the MFC and MPC of Manufacturing and Packaging.

Head- Production shall be responsible for approval of MFC and MPC.

Head-QA shall be responsible for final approval of MFC and MPC.

Head-QA and Plant Head shall be responsible for implementation and compliance of this SOP.

Procedure

The manufacturing or packaging procedures in the MFC and MPC shall be written in clear, easy to understand and unambiguous language.

MFC and MPC shall be generated on computer and shall be typed in font face ‘Times New Roman’ with font size ‘12’ (especially for the narrative text) printed on only one side of standard A-4 size white paper (with ‘landscape’ orientation) of appropriate quality in black ink

MFC detailing manufacturing procedure shall comprise of :

Weighment Sheet (format is given as Annexure-I and Annexure-II).

Manufacturing Instructions.

MPC detailing packaging procedure shall comprise of :

Packaging Order (format is given as Annexure-III).

Packaging Instructions

All pages of the MFC and MPC i.e. Weighment Sheet (Annexure-I and Annexure-II), Manufacturing Instructions , Packaging Order (Annexure-III) and Packaging Instructions  shall have the following information:

‘Product Code’; a unique numerical code assigned to the product by Doc. Cell . In case of MFC detailing manufacturing procedure (Annexure-1, Annexure-2 and Annexure-3), the three unique numeric characters (which shall always constitute the second, third and fourth characters of 10 characters Finished Product Code assigned as per SOP titled ‘Assigning Product Codes of Finished Products with batch size shall be mentioned here.

In case of MPC detailing packaging procedure (Annexure-4 and Annexure-5) Finished Product Code of Finished Products shall be mentioned under the column  ‘Product Code’.

‘Pkg. Formula No.’; Packaging formula number is a unique number given by the Packaging Development Scientist to a Packaging MPC in the form as ‘Location code – Product Code – Serial number which denotes pack size – Sales/Physician Samples etc.. – Market Code – Revision number’.

‘Supercedes’; the concerned scientist shall mention the superceded master formula number / packaging formula number against this column.

‘Master Formula No.’; Master formula number is a unique number given by the concerned Scientist in the form as – product code – batch size – revision number’.

‘Market’ for which the product shall be distributed.

‘Shelf Life’; the maximum assigned shelf life for the product in months shall be mentioned by the concerned scientist.

‘Effective Date’ is the date from which the implementation of MFC and MPC shall commence. The effective date in Day-Month-Year (DD-MM-YY) format shall be given by Quality Assurance, by hand after approval of the MFC and MPC.Its shall be revised as and when required.

‘Batch No.’ (Batch Number); At the time of issuance of BMR, which is an unfilled controlled photocopy of MFC and MPC along with relevant forms or attachments for recording purpose, Quality Assurance shall mention by hand/Machine the batch number of the product for which the MFC and MPC are to be issued, Batch Number shall be given as per SOP.

‘Mfg. Date’ (Manufacturing date) and ‘Exp. Date’ (Expiry date); Production shall fill the manufacturing date/ expiry date of the batch under these columns as per SOP titled ‘Procedure of Manufacturing and Expiry dates to the Finished products during Manufacturing.

In case of Packaging MPC, ‘Pack Size’ describes the type of pack and pack size e.g. Blister 10 x10’s,Glass Bottle 30 ml etc.

‘Page No’ (Page number); page number shall be mentioned in a running format i.e. first page of eleven page manufacturing instructions shall be written as 01 of 11 and 10th page shall be written as 10 of 11.

The weighment sheets and manufacturing instructions shall be numbered separately, in case of manufacturing MFC and in case of Packaging MPC, Packaging Order and Packaging Instructions shall be numbered separately.

‘Product Name’; the brand name of the product shall be mentioned. In case of Packaging Order and for Packaging Instructions for the physician sample, besides the brand name ‘PS’ shall be written.

‘Generic Name’; the Generic name of the product shall be mentioned.

‘Label Claim’; the label claim of the product shall be mentioned against this column. In case a product contains seven to eight actives, then the label claim, if not getting accommodated in the provided space, can be mentioned in a separate page giving cross reference of this page in this column and this page shall be the last page of the MFC and MPC (manufacturing/ Packaging). In case of tablets or other formulations, the colour(s) used can be mentioned underneath the label claim.

“Standard Batch Size” in case of Packaging procedure describing that materials shall be dispensed as per the standard batch size of the dosage form.

Tablets 200, 000 tablets (no. of strips),Capsules 200,000 capsules (no. of strips),Oral liquid         2000 liters liquid (no. of bottles),Injections 200 liters solution (no. of vials).

‘Actual Batch Size’, Batch size required for the packaging purpose.

Batch Size (In manufacturing procedure); Batch size of the product shall be mentioned e.g. for a batch size of 2.0 lakh tablets, the batch size shall be written as 2 00,000 tablets.

The designated persons or their designee from the mentioned department shall signature with name and date in the assigned columns as per responsibility mentioned.

All entries (except Batch No., Mfg. Date, Exp. Date, Effective Date, signatures with name and date of concerned persons for preparation, checking and approval, and Master Formula Number in Packaging Order and Packaging Instructions) shall be given by the scientist who is responsible for the preparation of MFC and MPC and hence shall be printed.

Note: All the entries shall be made in hand by using a good quality ball point pen preferably in Black ink.

Weighment Sheet (Annexure-I) shall contain all the relevant information related to dispensing of raw materials.

Following columns shall be printed (by the concerned scientist responsible for MFC’ preparation).

‘S.No’; Serial Number; each ingredient/ raw material shall be numbered.

‘Ingredient’; mention all the ingredients starting with Active(s) which shall be dispensed for use in manufacturing of the product. Raw material/ ingredient shall be written in such a way that these shall be dispensed as per their sequence of addition with respect to the quantity in the manufacturing process. The name of every ingredient shall be suffixed with its reference of specifications. Mention IP/BP/USP/USNF/Ph.Eur/IH, e.g. in case of Lactose with IP specifications, write Lactose IP.

Note: Weighment sheet shall be prepared in such a way that it can accommodate the scope of multiple weighing against one ingredient for its quantity and for its availability at Stores as different Batch Numbers.

‘Item Code’; mention item code assigned to the ingredient/raw material.

‘Qty/Unit (mg)’; Quantity per Unit in mg; this column head can be customized as per the requirement; mention as ‘Qty/cap’ or ‘Qty/tab’ or ‘Qty/10ml’ (in case of suspensions, etc.) or as ‘%w/w’ (in case of gelatin formula), etc.

‘Unit of Measurement’; Mention the unit in which the quantity shall be measured for dispensing e.g. kg, g, L, Nos. etc.

‘Standard Quantity per Batch’; It shall be a quantity required for the batch size. In case of dispensing the total batch quantity in lots, the same shall be mentioned in the weighment sheet e.g. if 50.0 kg of material is to be dispensed in 5 lots, the same shall be mentioned in column ‘Qty. /batch’ as 5 x 10.0 kg.

Following columns shall be filled (during the dispensing of raw materials by concerned person(s) of Production and Stores departments).

‘Required Quantity per batch to be dispensed’; after calculating the exact quantity of drug [active ingredient (s)], mention the quantity of active ingredient(s) to be dispensed along with other ingredients. If a quantity is being dispensed lot wise, in case of processing in multiple lots, then lot wise quantity (required) can be mentioned under this heading converting the title from to ‘Required Qty/ batch’ to ‘Required Qty (Lot -1)’, in case of dispensing for first lot and likewise. All other ingredients, which shall not be dispensed in lots, can be written on separate weighment sheet(s) under the heading ‘Required Quantity per batch to be dispensed’.

‘Ingredient Batch No.’; It is the batch number of the ingredient which is to be dispensed.

‘Quantity Dispensed’; Quantity dispensed shall be mentioned under Tare weight, Net weight and Gross weight notations.

Person responsible for dispensing of the material shall sign with date under the column ‘Dispensed by’ and person responsible for checking of dispensed material shall sign with date under the column ‘Checked by’

Note:  If a batch is being processed in different lots then the provision of dispensing of raw materials using separate weighment sheets for every lot can be given during preparation of MFC.

Dispensing of raw material shall be carried out as per the respective SOP of Stores department.

‘Page No.’ on weighment sheet (Annexure-1) shall be in continuation with ‘Page No.’ on weighment sheet (Annexure-II).

Weighment Sheet (Annexure-II) shall be a sheet of calculations, which shall be done to evaluate the actual quantity of active ingredient to be dispensed. Calculation shall be done considering the Assay and Loss on Drying (LOD) or Water content of the Active Ingredient(s), in percentage. Due to change in the quantity (ies) of Active Ingredient(s) the corresponding weight (batch weight) adjustments with another ingredient shall also be mentioned in this sheet.

Manufacturing Instructions  shall be covered under the following heads.

‘History’; mention ‘New’ for new MFC and MPC and in case of revision, the reason for revision from superseded version shall be mentioned in brief by the concerned scientist.

‘Precautions/ Instruction for manufacturing’; Proper handling of raw materials and other process related precautions shall be mentioned, however stage wise precautions, if any can also be given.

‘Checking of Weight/Volume’; weight/ volume of all the ingredients shall be checked against this column, by the production personnel.

While preparing MFC, Manufacturing Procedure shall be written with the interest of incorporating parallel information required/generating within the (execution of) MFC in following manner. Manufacturing procedure shall be detailed step by step giving reference of various SOPs or other reference documents, if available. The manufacturing procedure or steps involving processing shall be written in following manner (refer table given below).

Manufacturing Procedure Equipment/

Instrument Code

Process Time Done by Checked by
Start Over Sign Date Sign Date

Following columns as defined above, shall be filled during the manufacturing operations by the concerned production staff.

‘Equipment/ Instrument Code’; mention Identity number or code of the equipment/ instrument used

‘Process Time’; time taken to perform operations like mixing, drying, etc. shall be mentioned preferably by considering 24-Hour clock.

Persons responsible for performing the operations as per MFC and MPC shall sign with date in the columns ‘Done by’ and ‘Checked by’.

Mention the range of expected yield in percentage for relevant stage of manufacturing process. However for new products, the expected yield shall be based on knowledge of similar type of product. But after completion of five commercial scale batches, or first commercial campaign, the data shall be reviewed and if required, the necessary revision shall be made.

The ‘Packaging Order’ shall contain all the relevant dispensing information as specified in the respective format, for packaging materials.

Dispensing of packaging material shall be carried out in accordance with the relevant SOP.

Packaging Instructions shall be covered under the following heads.

‘History’; mention ‘New’ for new MPC and in case of revision, the reason for revision shall be mentioned by the concerned scientist.

‘Precautions’; packaging operation related precautions shall be mentioned. Stage wise precautions, if any can also be mentioned in the MPC under this heading.

‘Checking of Quantities’; Packaging material(s) dispensed as per Packaging Order shall be checked against this column, by the production people.

‘Overprinting Instructions’ required on the concerned packaging material shall be discussed under this heading.

While preparing MPC, Packaging Procedure shall be written with the interest of incorporating parallel information required/generating within the (execution of) MPC. Packaging procedure shall be detailed step by step giving reference of various SOPs or other reference documents covering various steps like primary packing, secondary packing tertiary packing, reconciliation of packaging materials and finished products including transfer of finished product to Quarantine Finished Goods Store and final yield, etc.

After preparing the MFC and MPC , a draft copy of the same shall be forwarded to QA for further evaluations/ review with respect to cGMP (Current Good Manufacturing Practices) standards, before finalization. The final draft of the MFC and MPC shall be forwarded to Head QA, Then, QA shall forward the same to R&D for necessary correction(s), if any. Draft copies shall be destroyed afterwards and finally take the print of MFC and MPC and approved by QA.

No column or row in the MFC and MPC shall be left blank and shall be appropriately filled by the production staff during recording against the defined procedure or instructions. Against no recording, write ‘NA’ or ‘Not Applicable’ in the relevant column and sign.

After approval of MFC and MPC, Head, QA or his / her designee shall put dates in ‘Effective Date’ column in DD-MM-YY format.

SOP titled ‘Document and Data Control’  shall be referred for preparation of Master copies and Controlled copies, distribution and retrieval of controlled copies, review and/ or revision of MFC and MPC.

All MFC and MPC shall be reviewed as and when required with change control procedure.

While issuing BPR (unfilled regulated copy of MPC for packaging) to Production, QA shall enter Master Formula Number in the column ‘Master Formula No.’ along with the entry for Batch number in Packaging Order and Packaging Instructions.

No column or row in the MFC and MPC shall be left blank and shall be appropriately filled by the production staff during recording against the defined procedure or instructions. Against no recording, write ‘NA’ or ‘Not Applicable’ in the relevant column and sign.

Forms and Records

  • Specimen Format for Weighment Sheet (dispensing sheet)-  Annexure-I
  • Specimen Format for Weighment Sheet (calculation sheet) –  Annexure-II
  • Specimen Format for Packaging Order – Annexure-III

Distribution

Master Copy – Documentation Cell (Quality Assurance)

Controlled Copies – Production, QA

History

Date Revision Number Reason for Revision
00 New

Annexure -I

Specimen Format for Weighment Sheet (dispensing sheet)

Contents:

  • Product Code
  • Master Formula No.
  • Market
  • Effective Date
  • Shelf Life
  • Batch No.
  • Mfg. Date
  • Exp. Date
  • Product Name
  • Generic Name
  • Label Claim
  • Batch Size
  • Ingredient
  • Item Code
  • Qty/Unit  (mg)
  • Unit of Measurement
  • Standard Quantity per Batch
  • Required Quantity per batch to be dispensed
    Ingredient
  • Batch No.
  • Quantity Dispensed : Tare weight/Net weight/Gross weight

Annexure -III

Specimen Format for Packaging Order

  • Product Code
  • Master Formula No.
  • Market
  • Effective Date
  • Shelf Life
  • Batch No.
  • Mfg. Date
  • Exp. Date
  • Product Name
  • Generic Name
  • Label Claim
  • Batch Size
  • Ingredient
  • Item Code
  • Qty/Unit  (mg)
  • Unit of Measurement
  • Standard Quantity per Batch
  • Required Quantity per batch to be dispensed
  • Quantity Dispensed : Tare weight/Net weight/Gross weight

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About Pharmaceutical Guidanace

Ms. Abha Maurya is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 18 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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