Procedure for Terminal Sterilization Validation

1) Purpose

The purpose of this SOP is to outline the procedure for validating terminal sterilization processes for pharmaceutical products to ensure microbial safety.

2) Scope

This SOP applies to all pharmaceutical products within the facility that undergo terminal sterilization as part of the manufacturing process, following regulatory guidelines and internal specifications.

3) Responsibilities

Quality Assurance (QA) Department: Responsible for overseeing and approving terminal sterilization validation activities.
Production Department: Responsible for executing terminal sterilization processes according to validated procedures.

4) Procedure

4.1 Protocol Development:
    4.1.1 Develop a Terminal Sterilization Validation Protocol outlining the objectives, methods, acceptance criteria, and responsibilities.
    4.1.2 Ensure the protocol complies with regulatory requirements and guidelines (e.g., FDA, EMA).

4.2 Sterilization Process Qualification:
    4.2.1 Conduct heat distribution studies (temperature mapping) to ensure uniform heat distribution throughout the sterilization chamber.
    4.2.2 Perform biological indicator (BI) studies using appropriate challenge organisms to demonstrate the sterilization efficacy.
    4.2.3 Validate the sterilization cycle parameters (e.g., temperature, time) based on worst-case scenarios.

4.3 Performance Qualification:
    4.3.1 Execute process simulations (media fill) using microbiological growth media to mimic actual production conditions.
    4.3.2 Monitor and analyze samples from media fills for microbial contamination post-sterilization.
    4.3.3 Ensure all performance qualification activities meet predetermined acceptance criteria.

4.4 Documentation and Report:
    4.4.1 Compile all data, results, and observations into a Terminal Sterilization Validation Report.
    4.4.2 Include detailed records of protocol execution, test results, deviations, and conclusions.
    4.4.3 Obtain QA approval for the validation report before implementation in routine production.

5) Abbreviations, if any

QA: Quality Assurance
BI: Biological Indicator

6) Documents, if any

Terminal Sterilization Validation Protocol
Terminal Sterilization Validation Report
Temperature Mapping Report
BI Studies and Results

7) Reference, if any

FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing
Pharmacopeial standards for terminal sterilization validation

8) SOP Version

Version 1.0