SOP on Site Master File (SMF) and How to prepare Site Master File as per guideline

Standard operating procedure on Site Master File  (SMF) is describes, What is a site master file and what are the requirements of the regulatory bodies while preparation of the site master file.

SOP on Site master file and how to prepare site master file

Standard  Operating Procedure (SOP) of  Site Master File  (SMF)


Purpose of this SOP is to provide a procedure for preparation and updation of Site Master File (SMF).

2.0 SCOPE :

Limited to Site Master File.


Production unit, Quality Assurance unit, Plant Head

4.0  DEFINITION           

4.1 Site Master File 

A site the master file is a manufacturer document containing truthful and specific GMP information about the production activity and control of manufacturing operations carried out by site or manufacturing unit and any closely joined operations at nearby buildings (facility).


5.1 Each manufacturing unit should have only one site master file (SMF per site).

5.2 If one site contains API as well as a formulation unit in such a case prepare SMF for both units separately.

5.3 If only a specific part of a pharmaceutical operation e.g. analysis, packaging. is carried out on the site. In such a situation site master file is required to describe only those operations.

5.4 A site master file should be brief and always print on A4 size pages and if possible, the site master file should not contain more than 25 pages.

5.5 Each page of the site master file (SMF) contains header on the top side. Header contains logo of manufacturer on the right top side, Site master file document number, version no., effective date, supersedes date, page number, prepared by, and approved by and next review date.

5.6 Site master file (SMF) numbering system

E.g.      SMF/AAA/BBB/001

SMF indicates Site master file

AAA indicates Site code

BBB indicates Unit code (If manufacture having two-unit API and Formulation on the same site)

001 indicates copy number

5.7 Minimum requirement of site master file (SMF) as per below (guideline):

5.7.1. GENERAL INFORMATION Contact information on the manufacturer.

a) Name of the manufacturer. The official address of the manufacturer.

b) Details of Name and street address of the manufacturing site, manufacturing buildings, and production units situated on the site.

c) Contact information of the manufacturer with 24-hour telephone number of the contact person in product defects or product recalls case.

d) Identification number of the site. For example, GPS details, D-U-N-S (Data Universal Numbering System) number of the site or any other geographic location system.

DUNS number a unique number having nine-digit, to identify for each physical location of your business. Authorized Pharmaceutical manufacturing activities of the site.

a) A copy of the valid manufacturing authorization like USFDA, TGA, MHRA issued by the relevant Competent Authority

b) Description of distribution, import, export, manufacture, and other activities as authorized by the relevant authorities / foreign authorities include authorized dosage forms/ activities respectively which is not covered by the manufacturing license.

c)  List product manufacturing on – site.

d) Enlist GMP audits or inspections of the site carried out within the last 5 years, including dates and names/country of the authorities having performed the inspection or audits. Any other manufacturing activities performed out on the site.

If any non-pharmaceutical activities performing on-site describe the activities. QUALITY MANAGEMENT SYSTEM OF THE MANUFACTURER The Quality Management System of The Manufacturer

a) Brief description of the quality management system carried out by the company and reference to the standards used.

b) Responsibilities related to the maintaining of quality system together with senior management.

c) Information of activities for which the site is accredited or certified, including date and contents of accreditations, names of accrediting bodies (accreditation means approval from regulatory bodies like USFDA, MHRA, EU, TGA, etc) Release procedure of finished products

a) Brief description of Authorized / Qualified Person requirements (education and work experience) who is responsible / accountable for batch certification and release procedures.

b) General description of batch certification and releasing the procedure of the product.

c) Role of qualified Person in quarantine. Role of authorized person release of finished products and in the assessment of compliance with the Marketing Authorization.

d) The setting between Authorized / Qualified Persons when numerous Authorized / Qualified Persons are involved.

e) Statement on whether the control strategy involves Real Time Release, Process Analytical Technology (PAT), and or Parametric Release. Management of suppliers and contractors

a) A summary of the establishment or knowledge of the supply chain and the external audit program.

b) Description of the qualification system of Vendors including contractors, manufacturers of API, and other critical materials suppliers.

c) Actions taken to ensure that products manufactured are compliant with Transmissible spongiform Encephalopathy (TSE)

d) Actions adopted where falsified product, bulk products (E.g. unpacked tablets), API, or excipients are identified.

e) Use of outside scientific, analytical, or other technical support in relation to manufacture or analysis.

f) Details of contract manufacturers and laboratories. Which includes details of Contract laboratories and manufacturers addresses, contact information and flow charts of supply-chains for outsourced manufacturing and Quality Control activities, e.g. testing of starting raw materials, packing etc.

g) Overview of the accountability/responsibility allocating between the contract giver and contract acceptor with respect to compliance with the Marketing Authorization. Quality Risk Management (QRM)

a)  Brief description of Quality Risk Management methodologies/strategy used by the manufacturer.

b) Scope and focus of Quality Risk Management with a description of any activities which are performed at the corporate level and those which are performed locally. Any application of the Quality Risk Management system to measure continuity of supply should be mentioned. Product Quality Reviews

Brief description of methodologies used.

5.7.2. PERSONNEL Organization chart/organogram required who show the arrangement for Quality management, production, and Quality Control positions/titles as well as including senior management and Authorized / Qualified persons. Number of personnel engaged in Quality management, Production, Quality Control, Storage, and distribution respectively.


a) Short description of the plant, size of the site (area of the site) and list of buildings.

b) Describing a simple plan of manufacturing area and scale of the plan (architectural or engineering drawings are not required).

c) Layouts and flow charts of the production areas need to show the room classification (Class A to D) and pressure differentials between connected areas and showing the production activities in the rooms.

d) Layouts of warehouses and storage areas as well as special areas for the storage, hazardous, highly toxic material, and sensitizing materials indicated, if applicable.

e) Brief description of the special storage conditions if applicable, but not indicated on the layouts.

f) Description of heating, ventilation, and air conditioning (HVAC) systems in brief.

  • Describe principles for air supply, temperature, humidity, pressure differentials, and air change rates, the policy of the air recirculation (%).

g) Brief description of water systems.

  • Quality Reference of water produced.
  • Schematic drawing of the systems 

h) Description of other related utilities such as steam, compressed air, nitrogen, etc.  Equipment

a)  List of major production and control laboratory equipment and instruments and identified critical pieces of equipment.

b) Cleaning and sanitation

  • Brief description of sanitization and cleaning methods of product in contact, surfaces cover manual cleaning, automatic clean in place, etc 

c) GMP critical computerized systems

  • Description of GMP critical computerized systems excluding PLCs specific equipment.

a) Description of documentation system (i.e electronic or manual).

b) Describe when documents and records are stored / archived off-site then the list of types of documents records, name and address of storage site and an evaluation of time required for retrieving documents from the off-site storage.

5.7.5. PRODUCTION Type of products

a) Types of products manufactured including

  • List of dosage forms of both human as well as veterinary products that are manufactured on the site.
  • List of dosage forms manufactured for any clinical trials (Investigational medicinal products) on the site. These investigational products are different from commercial manufacturing, information on production areas, and personnel.  

b) Toxic or hazardous substances are handled. For example, with high pharmacological activity and 1 or with sensitizing properties.

c) Types of products manufactured in a dedicated / devoted facility or on a campaign basis, if applicable. Process Validation

a) Describing general policy for process validation

b) Reprocessing or reworking Policy Material management and warehousing

a) System for the handling of starting materials (raw material), packing materials, bulk drug, and finished products including sampling, quarantine, release, and storage of products and materials.

b) Arrangements for handling of rejected products and materials.


Description of the quality control activities performed on the site in terms of physical, chemical and microbiological and biological testing.


Description of the mode in which the GMP compliance of the contract accepter is evaluated.

5.7.8. DISTRIBUTION, COMPLAINTS, AND PRODUCT RECALL Distribution (Only part of the manufacturer responsibility)

a) Types e.g manufacturing license holders, wholesale license holders, etc and locations (EU / EEA, USA, etc.) of the businesses to which the products are distributed and shipped from the site and the method of transport.

b) Description of the arrangement used to verify that each recipient/customer is legally permitted to receive/accept medicinal products from the manufacturer.

c) Brief description of the system to ensure appropriate environmental conditions during transit, for example, temperature monitoring/control.

d) Arrangement for product methods and distribution by which product traceability is maintained.

e) Actions were taken to avoid manufacturer products to fall into the illegal supply chain. Complaints, product defects and recalls

Brief description of the system for handling product defects, complaints, and recalls.


Short description of the self-inspection (Internal audit) arrangement includes attention on criteria used for selection of the areas which covered during planned inspections by manufacturer, practical arrangements, and follow up activities.


Annexures attached to site master files such as layouts, diagrams, photographs, product lists, organization charts (Organogram), etc. should be listed. Annexures should not be numbered in continuation of the page numbers of the site master file.

Annexure the page numbering system is separate for each annexure.


The short forms/acronym used in the site master file should be listed here.

5.7.12  Any additional information required to be included in the site master file based on the guidelines from the regulatory agency, for example, site photographs, product list, etc. should be attached as annexures to the site master file.

5.7.13  Each page of the site master file should be signed on and dated on left bottom corner by the person who has compiled the site master file.

5.7.14  Site Master File should be reviewed after every 2 years or earlier if required.

5.7.15   Any changes in the Site Master File should go through a change control procedure.

5.7.16 If required, photocopy of the Site Master File should be made and stamp as “CONTROLLED COPY” with green ink.

5.7.17    It is the responsibility of the Unit / The organisation to keep track of the updation in the site master file.


7.1 PICs guidance Explanatory notes for Pharmaceutical Manufacturers on the preparation of the site master file-2011

7.2 WHO ‘TRS 961 – WHO guideline for drafting a Site Master File

7.3 Eudralex guidance, volume 4: Explanatory notes for Pharmaceutical Manufacturers on the preparation of site master file


Not Applicable


1. What is a site master file?

A site the master file is a manufacturer document containing truthful and specific GMP information about the production activity and control of manufacturing operations carried out by site or manufacturing unit and any closely joined operations at nearby buildings (facility).

2. How many pages should a site master file be?

As per European guidelines, the site master file must have sufficient information. However, it is possible not to use more than 25-30 pages to write the information, plus annexures. Annexures attached to site master files such as layouts, diagrams, photographs, product lists, organization charts (Organogram), etc. should be listed. Annexures should not be numbered in continuation of the page numbers of the site master file.

3. Is a site master file (SMF) required?

Yes. The site master file is part of the regulatory guideline (requirement). It covers data related to company General Information, Quality Management system of a company, Personnel Information, Premises and equipment information, Documentation, Production inf0rmation, Quality control system, Contract manufacturer and laboratory details, Product distribution, recall and complaint details, Self Inspection details. The site master file is specific good manufacturing practices information.

Leave a Reply

Google Translate »
error: Content is protected !!