OBJECTIVE:

• The purpose of this Standard Operating Procedure (SOP) is to define the procedure for the preparation, review, approval, distribution, and control of the Site Master File (SMF) in accordance with the requirements of WHO / TRS / EU-GMP Part III and other applicable regulatory guidelines.
•  The SMF provides a detailed overview of the site’s quality management system, facilities, utilities, and manufacturing operations to demonstrate GMP compliance.

SCOPE:

• This SOP applies to all manufacturing, testing, and packaging facilities of the company engaged in the manufacture and control of pharmaceutical products. It covers the initial preparation, periodic review, and update of the SMF.

RESPONSIBILITIES:

Quality Assurance (QA):

• Shall responsible for drafting, reviewing, updating, and maintaining the current version of the SMF.
• Shall ensures alignment of the SMF with EU-GMP / WHO TRS requirements and company procedures.

Department Heads:

• Department Heads of Production, Quality control (QC), Engineering, Warehouse, Human Resource (HR), Environment Health and Safety (EHS), Shall provide required departmental information, data, and updates for inclusion in the SMF.

 Quality Head:

• Shall responsible for final approval and authorization of the SMF before issue to regulatory authorities or customers.

DEFINATIONS:

• SMF: A document describing the quality management system of the manufacturer, the production and/or control of pharmaceutical manufacturing operations, and any closely integrated operations carried out at the same site.
• Controlled Document: A document issued, approved, and managed under the document control system ensuring traceability and version management.
•  Uncontrolled Copy: Copy issued for information or regulatory submission only.
•  Major Change: Modification that can affect product quality, GMP status, or regulatory commitments.

PROCEDURE:

Preparation:

• QA shall draft the SMF using the EU-GMP Part III format / WHO TRS, including the following sections:
  • • • General Information & Site Overview
        • Site name, address, GPS coordinates
        • Organization structure and key personnel
        • Manufacturing license and certifications
        • Site layout and area classification
        • Reporting Structure

Quality Management System:

• • QA policy, document control, deviation, CAPA, change control
  • Self-inspection and management review systems.
  • Recall system.
  • Complaint handling,
  • Supplier Qualification

Personnel

• • Organizational hierarchy and training systems

Premises and Equipment

• • Facility description with material/personnel flow diagrams
  • Approved critical equipment list

HVAC System

• • Area classification (ISO grades)
  • Design type (recirculation, once-through)
  • Pressure differentials and monitoring system
  • Maintenance and validation frequency

Utilities and Support Systems

• • Water Treatment Plant (WTP), Distribution loop diagrams, monitoring, and control philosophy.
  • Compressed Air.
  • Power Supply and Power Back up.
  • Calibration data.

Documentation

• • Master Formula.
  • Batch Records,
  • Specifications
  • Approved Product List.

Production

• • Dosage forms manufactured
  • Process flow diagrams and key controls

Quality Control

• • Testing facilities.
  • Approved Instruments List,
  • Brief on Method Validation,
  • Brief on Reference standards

Warehouses

• • Brief on Warehouse Practices
  • Brief on FIFO/FEFO System
  • Product receipt procedure

Appendices and Drawings

• • Site layout.
  • HVAC schematic,
  • water system diagram.
  • Effluent Treatment Plant Diagram
  • Preventive Maintenance Schedule
  • Product Quality Review
  • Validation Planner
  • Qualification Planner
  • Self-Inspection Planner
• Each department shall provide updated data, layout drawings, and lists of key equipment as applicable.

Review and Approval:

• QA shall circulate the draft SMF to respective departments for content verification.
• After consolidation, QA shall submit the final version to the Quality Head for approval.
• The approved SMF shall be assigned a revision number and effective date.

Distribution and Control:

• QA shall issue controlled hard and soft copies to the QA Master File and designated regulatory folders.
• Controlled copies and uncontrolled copies for outline circulation shall be recorded in the document distribution log.

Revision and Frequency:

• The SMF shall be reviewed every three years or immediately after any major change affecting facility, product range, or Quality Management System (QMS).
• All changes shall be documented in the revision history section and approved by QA.

Archival:

• Obsolete versions shall be stamped “OBSOLETE COPY” and archived for at least five years from the date of supersession.
• Only the latest approved version shall remain active.

Numbering System:

• Each SMF shall carry a unique identification number using the following pattern: SMF/YY/XXX, where:
  • • SMF = Site Master File identifier
    • YY = Last two digits of the year of issue
    • XXX = Sequential serial number starting from 001
    • Example: SMF/25/001

REFERENCE:

• EU Guidelines to Good Manufacturing Practice – Part III (Site Master File)
• WHO TRS 961, Annex 14 – Guidance on Preparation of a Site Master File

RECORDS:

 REVISION HISTORY: