Site Master File (SMF)

SMF (Site Master File) as the name indicates is a document that provides authentic information regarding the site of a pharmaceutical manufacturing plant. The document is prepared by the pharmaceutical manufacturer with complete information regarding the policies and activities including all the operations related to production, quality control at the site or any other relevantly linked operations carried out at adjacent or nearby buildings. If only a part of operation is carried out at the particular site than document must only contain the specified information regarding the activity conducted at the site, for Example: Labeling

Common features of a Site Master File:

• It should contain all the information regarding the GMP activities carried out at the pharmaceutical plant which is necessary for regulatory requirements.
• The document should have all the adequate information but not be a massive one. It should be tried to provide all the information within 25-30 pages including the appendices.
• Drawings and layouts are more preferred rather than narratives.
• The layouts and designs should be clear and readable when printed on A4 sheets.
• The document should be a part of Quality Management System and should be prepared with proper edition number,effective date and  reviewed according to the policy of the documentation (as per SOP on Document Control).
• It should always be up to date with all the current activities carried out at the site.

The format for Site Master File varies from country to country but the general format almost remains the same which include the following:

• General Information of the manufacturer
• Quality Management System
• Personnel
• Premises and  Equipment
• Documentation
• Production
• Quality Control
• Contract Manufacture, analysis and other services
• Post Operational Activities
• Self inspection
• Export of drugs

A) GENERAL INFORMATION OF THE MANUFACTURER: 

• CONTACT INFORMATION:

1. Name and official address of the manufacturer both official (of site) and unofficial.
2. Contact Information of the manufacturer with 24 hours telephone service available.
3. Unique identification number of the site.

• INFORMATION REGARDING THE ACTIVITIES (AUTHORIZED AND OTHERS) CARRIED OUT AT THE SITE

1. Valid copy of authorization from the competent authority or reference number from EudraGMP database which ever is available.
2. Brief description of manufacture, import, export, distribution and other activities as authorized by the relevant Competent Authorities including foreign authorities with authorized dosage forms/activities, respectively; where not covered by the manufacturing authorization;
3. Type of products currently manufactured on-site.
4. List of GMP inspections of the site within the last 5 years; including dates and name/country of the Competent Authority having performed the inspection.
5. A copy of current GMP certificate or reference to the EudraGMP database, should be included, if available.
6. List of any other activities carried out at the site (non- pharmaceutical).

B) QUALITY MANAGEMENT SYSTEM: 

Brief description of the quality management systems, reference of standards, responsibilities of senior management, accreditation dates, contents and names of accrediting bodies should be incorporated in SMF.

• RELEASE PROCEDURE OF FINISHED PRODUCTS:

1. Description of release strategy (Real Time or Parametric Release)
2. Qualification requirements of the authorized persons responsible for batch release.
3. General procedure of release of batch with proper certification.
4. Description of role of persons associated with the quarantine or release of finished product and in assessment of compliance with the marketing authorization.
5. Description of release strategy (Real time or parametric release).

• QUALITY RISK MANAGEMENT:

1. Brief description of QRM methodologies used by the manufacturer.
2. Scope of the QRM methodologies both at corporate or local levels.

• PRODUCT QUALITY REVIEWS:
  – Brief description of methodologies used for the product quality reviews by the manufacturer

C) PERSONNEL:

1. Organisation chart describing the important personnel involved.
2. Qualification, experience and responsibilities of the key personnel.
3. Training documents of all the personnel involved both basic and in service.
4. Health requirements of personnel engaged in manufacturing.
5. Any specific color code or uniform for personnel.

D) PREMISES AND EQUIPMENT:

1. Short description of the facility, size and list of buildings (for example if the production is according to the separate markets like local, EU, USA etc).
2. Brief description of manufacturing area with indication of scale.
3.  Layouts and flowcharts of production areas, warehouses, storage units, adjoining rooms etc.
4. Brief description of the HVAC system installed and specifications of the factors.
5. Brief description about the water system with quality reference standards for the water produced.
6. Brief description regarding the relevant utilities such as steam, compressed air, nitrogen etc.
7. List of all the major equipments for production and QC area.
8. Calibration system.
9. Sanitation.

E) DOCUMENTATION: 

1. Description of the documents whether electronic or manual.
2. Preparation, Revision and Distribution of documents.
3. List of documents, storage site, numbering system all must be defined.
4. Procedure of archiving of documents.

F) PRODUCTION: 

1. The type of products being manufactured including the list of dosage forms (human, veterinary and investigational medicinal product).
2. Brief description of the production operations (filling, mixing, granulation, punching, labeling etc.).
3. Handling of the materials: any hazardous chemicals or products being handled should be mentioned in SMF with all the precautions.
4. Arrangements for the handling of starting materials, packaging materials, bulk and finished products including sampling, quarantine, release and storage.
5. Handling of the rejected materials or products.
6. Brief description of general policy for process validation, reprocessing or reworking.

 G) QUALITY CONTROL: 

Description of quality control activities carried out at the facility including all the physical, chemical, biological or microbiological testing. Standard testing procedure formats and any other relevant information should be mentioned in SMF.

H) CONTRACT MANUFACTURE AND ANALYSIS AND ANY OTHER SERVICES: 

1. Procedure for the selection and qualification of the contractors, manufacturers or any other vendors.
2. Specific measures taken to analyse the counterfeit/falsified products, bulk products, active pharmaceutical ingredients or excipients.
3. Any services like analytical assistance taken from the outsources should be mentioned.
4. Overview of the responsibilities between the contract giver and acceptor owing to all the marketing Authorization.

I) POST OPERATIONAL ACTIVITIES:

1. PRODUCT DISTRIBUTION AND HANDLING OF PRODUCT COMPLAINTS: The chain  of supply should be clearly mentioned with the use of flowcharts. Tractability should be such that if any market compliant is filed it should be easily detected. The types whether whole sale or manufacturing licences holders and sites of distribution should be clearly mentioned. Description of the system used to verify that each customer / recipient is legally entitled to receive medicinal products from the manufacturer.
2. PRODUCT RECALL: Brief description of the system for handling of complaints, product defects and recalls.

J) SELF INSPECTIONS: 

Short description of the self inspection system with focus on criteria used for selection of the areas to be covered during planned inspections, practical arrangements and follow-up activities.

In addition to all the points above Schedule M has incorporated some more points as guidelines for preparing the Site Master File which include EXPORT OF DRUGS: Description of the products exported to different countries.