Site Master File

Overview

The Site Master File (SMF) is prepared by pharmaceutical manufacture and it should contain specific information about quality polices and activities of the site, the production and/or quality control of pharma manufacturing activities at site.

SMF Should provide the clear information on the manufacturer's good manufacturing practices (GMP) related activities that can be useful for planning and for GMP inspection by regulatory authorities.
SMF should be part of documentation belonging to the quality management system (QMS) of manufacturer and kept updated. SMF contain sufficient information however possible not exceed 25-30 pages plus appendices or attachments.The SMF should be part of documentation belonging to quality management system of the system of the manufacturer and kept updated accordingly. It should be regularly review to ensure that it is up to date.

Content of Site Master File:

1.  General information on the manufacture

• Contact information on the manufacturer:
• Name and official address of the manufacture, street addresses of the suit, building and production unit located on the site.
• Contact information of manufacturer including 24-hour telephone number of the contact personnel in the case of product defects or recalls and
• Global positioning system (GPS) details, Data Universal Numbering System (DUNS) number of the site.

• Authorized pharmaceutical manufacturing activities of the site: 
• Copy of valid manufacturing authorization issued by the relevant authority (Annex 1).
• Brief description of manufacture, import, export, distribution and other activities as authorized by authority.( including external agencies)
• List of product currently manufactured on-site (Annex 2).
• List of GMP inspection of the site within last five years; including dates and name/country of the authority having performed the inspection. A copy of the current GMP certificate (Annex 3).
• Description of non pharmaceutical activities.

     2. Quality Management:

• Quality system of the manufacturer

•  Brief description of the quality management system run by the company and standards used.
• Responsibilities related to the maintaining of the quality system including senior management
• Information and activities for which the site is recognized and certified, including dates and content of accreditation, and name of accrediting bodies. 

• Release procedure of finished product.

• Detail description of education and work experience of the authorized person(s) responsible for batch releasing.
• General description of batch release procedure.
• Arrangement between authorized persons when several authorized person are involved

• Management of supplier and contract.

• A brief summary of the establishment of supply chain and the external audit programme, qualification system of contractors, manufacturers of APIs and other critical material suppliers.
• Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis. List of contract manufacture and laboratories including the addresses. (Annex 4)
• Brief overview of the responsibility sharing between the contract giver and acceptor.

• Quality Risk Management (QRM)

• Scope of QRM including brief description of any activities which is performed at corporate level, and those which are performed locally. Describe QRM methodologies used by manufacture.

• Product Quality Review

• Brief description of methodologies used.

• Personnel

• Organization chart showing the arrangements for quality management, production and quality control position (in Annex 5), including senior management and authorized/qualified person and number of employees engaged in Quality, production, storage and distribution

• Premises and Equipment

• Premises
• Short description of plant size of the site and list of buildings.
• Simple plan or description of manufacturing area with indication of scale.
• layout and flowcharts of production area showing the room classification and pressure differential between adjoining area and indicating the production activities. (Annex 6)
• Layout of warehouse and storage areas.
• Brief description of HVAC system :- Principles of air supply, temperature, humidity, pressure differentials and air change rates policy of air recirculation (%).
• Brief description of water system :- Quality reference of water produced and schematic drawing of the system. (Annex 7)
• Brief description of other relevant utilities such as steam, compressed air, nitrogen etc.
• Equipment
• list of major production and control laboratory equipment with critical pieces of the same equipment. (Annex 8).
• short description of cleaning (i.e. manual, automatic clean-in-place, etc.) and sanitation method of product contact surfaces.
• Good manufacturing practices critical computerized systems (excluding equipment specific PLCs).

• Documentation

• Description of document system (i.e. electronic, manual). requirement of document and records archival.

• Production

• Type of product manufactured (both human and veterinary product) manufactured at site.
• product type manufactured in a dedicated facility or on a campaign basis (if applicable).

• Process validation

• General policy for process validation and reprocessing or reworking.

• Material management and warehousing

• Arrangements for starting materials, packing materials, bulk, finished and rejected materials and products.

• Quality control 

• description of the QC activities carried out on the site in term of physical, chemical, microbiological and biological testing.

• Distribution, complaints, product defects and recalls.

• Distribution :- types and location to which products are shipped from the site. Description of system to ensure appropriate environmental condition during transit. Arrangements of product distribution and method by which product tractability is maintained.
• Complaints, product defect, and recalls :- Description of the system for handling complaint, product defects and recalls.

• Self inspections

• Description of the self- inspection system with focus on criteria used for selection of the areas to be covered during planned inspections and follow up activities.

• Annexes to be submission of a site master file

          Annex 1 Copy of valid manufacturing authorization
          Annex 2 List of dosage forms manufactured including the International Non-proprietary                                     Names (INN) or common name (as available) of APIs used.
          Annex 3 Copy of valid GMP certificate
          Annex 4 List of contract manufacturers and laboratories including the addresses and contact                               information, and flowcharts of the supply chains for these outsourced activities
          Annex 5 Organizational charts
          Annex 6 Layouts of production areas including material and personnel flows, general                                         flowcharts of manufacturing processes of each product type (dosage form)
          Annex 7 Schematic drawings of water systems
          Annex 8 List of major production and laboratory equipment.

 
Reference:

• WHO guidelines for drafting a site master file- Annex 14
• Explanatory notes for Pharmaceutical Manufacturers on the preparation of Site Master File” PIC/S, PE 008-4, 1 January, 2011