Preparation Approval Control and Distribution of Master Formula Records

1.0 OBJECTIVE :
1.1 To lay down a procedure for preparation, approval, control and distribution of Master Formula Records for manufacturing as well as packing of finished pharmaceutical products.

2.0 SCOPE :
2.1 This procedure is applicable to preparation, approval, control and distribution of Master Formula Records for manufacturing as well as packing of finished pharmaceutical products at abc company.

3.0 RESPONSIBILITY :
3.1 Officer/Executive of Production Shall be responsible for initiating /preparation of Master Formula Record
3.2 Manager of production department shall be responsible for review.
3.3 QA Head shall be responsible for review and approval of Master Formula Record.
3.4
4.0 ACCOUNTABILITY:
4.1 Production Head and QA Head.

5.0 PROCEDURE :
5.1 PREPARATION OF MASTER FORMULA RECORD OF NEW PRODUCT (NOT MANUFACTURED)
5.2 Officer/Executive Production shall prepare the master Formula record.
5.3 Officer/Executive/Manager of production shall check the MFR, if any correction is required send back to officer/ Executive for correction. If satisfactory, he/she shall send the same to QA for approval with sign/date.
5.4 Manager QA shall approve the Master Formula Record
5.5 REVISION OF MASTER FORMULA RECORD OF EXISTING PRODUCT
5.6 Officer/Executive/Manager of Production shall be responsible to fill the change control and amendment in MFR in case of following changes.
5.7 (A) Change in bill of material.
(B) Change in bill of primary Material
(C) Change in sequence of mixing.
(D) Change in Critical process parameter e.g. mixing time, drying time/temp etc. .
(E)Change in Batch size.
(F)Change in Pharmacopoieal status.
(G)Change in Primary packing material
(H)The remaining other changes that have not been mentioned.
5.7.1 PREPARATION OF MASTER FORMULA RECORD
5.8 Officer/Executive Production shall prepare MFR as per Annex-I and below guideline.

5.9 The page setting conforms to the following guideline

1.1 Paper Size	1.2 A4 Size
1.3 Top Margins	1.4 0.75”
1.5 Bottom Margins	1.6 0.50”
1.7 Left Margins	1.8 0.50”
1.9 Right Margins	1.10 0.50”
1.11 Gutter	1.12 0”
1.13 Header from edge	1.14 0.5”
1.15 Footer from edge	1.16 0.5”

5.26 The text of MFR conforms to the following guideline

1.1 Language	1.2 English
1.3 Translation language (if applicable)	1.4 Regional language
1.5 Grammar	1.6 Active/Present
1.7 Font Type, Size (Header)	1.8 Times New Roman, Bold/ 12pt.
1.9 Font Type, Size (Footer)	1.10 Times New Roman, Bold/ 12pt.
1.11 Font size (Sections)	1.12 Times New Roman, Bold / 12pt.
1.13 Font Type, Size (Text)	1.14 Times New Roman, plain / 12pt.
1.15 Printing (one side or two sides)	1.16 One side

5.43 Header shall have following details,
5.44 Department: Type name of the department viz. Liquid, Ointement or Parentral product to which the product belongs.
5.45 Product Name: Type name of product which shall be mentioned in product permission.

5.46 Standard Batch Size: Type the standard batch size in no.
5.47 MFR No.: Type MFR no. in the form of FPPL/MFR/XX/YYY-ZZ, where MFR indicates Master FORMULA RECORD, XX indicates department code, YYY indicates finished product code , ZZ indicates version no. of MFR which shall starts from 01.
5.48 FOR EXPORT: Type MFR no. in the form of FPPL/MFR/E/YY-ZZ, where MFR indicates Master Formula Record, E indicates EXPORT, YY indicates finished product code , ZZ indicates version no. of MFR which shall starts from 00
5.49 Page No.: Page number indicates serial no. of pages in “x” of “y” pattern

5.49.1 Effective Date: Give the date on which MFR is going to be effective. It shall be hand written by QA after QA Head approval on MFR.
5.49.2 Effective B. No.: Give the batch no. of the product from which MFR is going to be effective. It shall be hand written by QA which shall be the next batch of batch allocation register.
5.49.3 Supersede No.: This number indicates the previous MFR no. when that MFR is changed or reviewed and new version no. is allocated. e.g. if MFR no. FPPL/MFR/PL/001-01 is revised and new MFR no. is allocated as FPPL/MFR/PL/001-02, then Supersede No. of revised MFR shall be 01 which indicates revision no. If any MFR is prepared first time i.e. with 00 version no., put ‘NIL’ in Supersede No. column.
5.49.4 Prepared By: Officer/Executive Production shall prepare MFR, sign here and write the date.
5.49.5 Checked By: Production/Packing head shall check MFR and if found satisfactory he/she shall sign here and write the date..
5.49.6 Approved By: QA head shall review MFR and if found satisfactory he/she shall sign here and write the date.
5.50 Type content of MFR in the following sub-headings:
1.0 PRODUCT INFORMATION
2.0 TABLE OF CONTENT
3.0 FLOW CHART FOR FORMULATION
4.0 BILL OF RAW-MATERIAL
5.0 BATCH MANUFACTURING PROCESS
6.0 YIELD AND ACCOUNTABILITY

1.0 PRODUCT INFORMATION: Type as below:
• Product code: Indicates finished product code.
• Product (Brand) name: Type name of product which shall be mentioned in product permission.
• Generic name: Shall be typed as ‘API name – Dosage form – Pharmacopoeial status (if any) – Strength of product’.
• Label claim: Type label claim which shall be mentioned in product permission.
• Primary Pack Description: Description of primary packing material e.g. 1 ml amber glass USP type I ampoule with blue ring, pet bottle and amber colour glass ampoule.
• Product Description: Description of product e.g. clear colour solution..
• Shelf-life: Type shelf life of the products in months.
• Storage Condition: As per Trial batches stability data as well as Pharmacopoeial recommendation.
2.0 TABLE OF CONTENT: Type as below:

Sr. No.	Contents	Page No.

FLOW CHART FOR FORMULATION: Shall have the flow chart of major steps of formulation along with critical parameters and precautions

4.0 BILL OF RAW-MATERIAL: Type as per approved master card and below table:

Sr.

No.

Ingredients

Pharmacopoeial

Status

Label claim

Standard Qty(kg)

Overages

(%)

Batch

Qty/ (Kg)

Type standard batch size specific ‘Qty/batch’. Below this table, give the formula for batch calculation of each ingredient mentioned in label claim. Also give example for calculation of each ingredient required per batch. API quantity required per batch shall be calculated considering ‘as is’ basis assay to compensate the quantity of moisture/water content and/or impurity content in API so as to formulate the batch to provide not less than 100 percent of the labeled amount of API.

5.0 BATCH MANUFACTURING PROCESS:
• Type the instructions of each critical stage of manufacturing required for the product.
• Before commencing process, take area/line clearance from QA.
• Type standard batch size specific instructions.
• Give reference SOP No. wherever applicable.
• Give instruction to monitor critical parameters (viz. temperature, relative humidity, pressure, dissolved oxygen content, duration in minute, revolution per minute etc) and record the same in to BMR.
• Give instruction about in-process quality checks to be carried out along with sampling procedure, frequency and acceptance criteria.

6.0 YIELD AND ACCOUNTABILITY: Type as below:

No.	Stage/Parameter	Unit	Method	Limit

In case of actual yield is out of above mentioned limit, Officer/Executive/Manager of production/packing department shall fill the deviation form and get it approved by QA Head

5.51 SPECIAL PRECAUTION: Enlist the special precautions on last page of MFR which must be taken care of during manufacturing of the product viz. precautions to be taken for sensitive (light, moisture, oxygen and/or temperature), hold time between critical manufacturing stages, etc.
5.52 CONTROL AND DISTRIBUTION OF MFR
5.53 Executive or designee QA shall stamp “MASTER COPY” (red in color) on the right side of all pages of approved MFR.
5.54 At the same time, Officer / Executive of QA shall prepare and maintain the master list (in computer-copy) of MFR of all departments which shall following columns:
• List updated on
• Serial No.
• Product name
• Generic name
• Shelf life
• MFR no.
• MFR effective date
• MFR effective B. No.
• BMR No.
• BMR effective date
• BPR No.
• BPR effective date
5.54.1 Only Officer/Executive of QA shall retain computer copy of MFR of all departments. QA department as a custodian shall retain this “MASTER COPY”.
5.54.2 If Required Officer/Executive QA shall take photocopies of “MASTER COPY” of MFR and stamp the photocopy of MFR as “CONTROLLED COPY” (Blue in color) on each page in the space provided for the same in the header of MFR. “CONTROLLED COPY” stamp “Sign./Date”.
5.54.3 Officer/Executive QA shall record the number of the copy to be distributed in Annex-II QA/001-A-II-01 (Controlled document distribution, retrieval and destruction record) of SOP No. FPPL/QA/001-01 shall write the same number in “CONTROLLED COPY” stamped on MFR.
5.54.4 Officer/Executive QA shall forward above MFR copy to concern department. Officer/Executive QA shall get the acknowledgement of that department. He / She shall maintain this distribution records Annex-II QA/001-A-II-01 (Controlled document distribution, retrieval and destruction record) of SOP No. FPPL/QA/001-01 along with MASTER COPY document.
5.54.5 Concerned department shall refer MFR distributed by QA with “CONTROLLED COPY” stamp and in no case MFR without stamp shall be referred/ used by that department.

5.54.6 In case if a copy of MFR are required to be given to outside agency, its photocopying of controlled copy (by seeking department) shall be done with permission of Head QA. QA person shall stamp “UNCONTROLLED COPY” in red ink on bottom of each page of MFR.
5.55 WITHDRAWAL OF CONTROLLED MFR
5.55.1 At the time distribution, Officer/Executive QA shall retrieve and destroy all distributed controlled copies of previous revision of MFR by shredding into the small pieces. Officer/Executive QA shall maintain record of the same in Annex-II (Controlled document distribution, retrieval and destruction record) of SOP No. QA-001.
5.55.2 Officer/Executive QA then shall stamp “OBSOLETE” in red ink on center of all pages of “MASTER COPY” of MFR.
6.0. ABBREVIATION :

Sr. No.	Abbreviation used	Full form of abbreviation used
1.0	SOP	Standard Operating Procedure
2.0	w.r.t.	With respect to
3.0	MFR	Master Formula Record
4.0	BMR	Batch Manufacturing Record
5.0	BPR	Batch Packing Record
6.0	Ref.	Reference
7.0	QA	Quality Assurance department
8.0	API	Active Pharmaceutical Ingredient

ATTACHMENTS (ANNEXES) :
Annex-I : Master Formula Record format
8.0. REFERENCE :

Sr. No.	Reference Title
1.0	Schedule M (Good Manufacturing Practices and Requirements of Premises, Plant and Equipment for Pharmaceutical Products)
2.0	Quality assurance of Pharmaceuticals, A compendium of guidelines and related materials, Volume 2, ,
3.0	Guide to Good Manufacturing Practice for Medicinal Products

QUALITY ASSURANCE

Master Formula Record Format

MASTER FORMULA RECORD (FORMULATION SECTION)

Company Name	Department :	MFR No.: MFR-
	Product Name:	Page No.:
		Effective Date:
	Standard Batch Size:	Effective Batch No.:
		Supersede No.:

1.0. PRODUCT INFORMATION :

Product Code
Product (Brand) Name
Generic Name
Label Claim




Primary Pack Description
Product Description
Shelf-life
Storage Condition

2.0. TABLE OF CONTENT :

Sr. No.	Contents	Page No.

3.0. FLOW-CHART FOR FORMULATION :

4.0. BILL OF RAW MATERIAL :

Sr.

No.

Ingredients

Pharmacopoeial

Status

Label claim

Standard Qty(kg)

Overages

(%)

Batch

Qty/ (Kg)

Type standard batch size specific ‘Qty/batch.Below this table, give the formula for batch calculation of each ingredient mentioned in label claim. Also give example for calculation of each ingredient required per batch. API quantity required per batch shall be calculated considering ‘as is’ basis assay to compensate the quantity of moisture/water content and/or impurity content in API so as to formulate the batch to provide not less than 100 percent of the labeled amount of API.

5.0. BATCH MANUFACTURING PROCESS

6.0. YIELD AND ACCOUNTABILITY :
Calculate the % yield at various stage

QUALITY ASSURANCE

Master Packing Record Format

MASTER PACKING RECORD (PACKING SECTION)

Company Name	Department :	MFR No.: MPR-
	Product Name:	Page No.: 1 of 2
		Effective Date:
	Standard Batch Size:	Effective Batch No.:
		Supersede No.:

PRODUCT INFORMATION :

Product Code
Product (Brand) Name
Generic Name
Label Claim




Primary Pack Description
Product Description
Shelf-life
Storage Condition

2.0. TABLE OF CONTENT:

Sr. No.	Contents	Page No.

3.0. PACKING MATERIAL REQUIREMENT AND PROCEDURE: Type the packing material requirement as per below table:

Sr. No.	PM Code	Packing Material	Excess quantity (%)	Total quantity per batch*

Type standard batch size specific ‘Total quantity per batch’, if more than one standard batch size are finalized.
* Issued quantity may vary with the actual yield

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sop for performance qualification for analyst

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