Guideline for the Validation of Aseptic Process

Table of Content:

1. Purpose

2. Scope

3. Safety

4. References

5. Introduction

6. Pre-requisites for Aseptic Process Validation (Media Fills)

7. Frequency and Requirements for Challenges

7.1. New Production Lines

7.2. Changes to Existing Production Lines

7.3. Routine Re-validation of Aseptic Filling Lines

7.4. Facility Shutdowns and Recommissioning

7.5. Routine Clean Room Classification

8. Production Records

9. Duration of the Run and Number of Containers to be Filled

9.1. Duration

9.2. Size of runs

9.3. Filling

10 Simulation Conditions

10.1 Aseptic Processing Operators and Support Personnel

10.2 Procedures

10.3 Equipment – Maintenance and Breakdown Simulation

10.4 Environmental Monitoring

11. Media

12. Inspection and Incubation of Filled Containers

13. Validation Report of Aseptic Processing

14. Acceptance Criteria and Responses

14.1 General Requirements

14.2 PIC’S – Acceptance Criteria

14.3 Other – Acceptance Criteria

14.4 Notification of a Media Fill Out of Specification (OOS)

15. Cancelling of Process Simulation Runs

16. Reference Documents

Sample Content

    1. PURPOSE

The purpose of this document is to provide a set of guidelines to be used when determining a suitable approach for the qualification of aseptic processing validations at the manufacturing facility involving in aseptically filled medicinal products.

2. SCOPE

These guidelines provide suggestions and considerations for the design and preparation of aseptic media fill validations protocols and reports. They are intended to be used as guidelines only, alternative approaches for validation may be appropriate and can be used provided that the principals of validation as outlined in the company Validation Master Plans are followed.

Out of scope are closed aseptic processing systems where no aseptic connections are made post sterilisation and temperature and pressure are monitored during Steam In Place (SIP) sterilisation.

3. SAFETY

All safety requirements for relevant production areas must be followed at all times.

4. References

PICS 2009 Guide to Good Manufacturing Practice for Medicinal Products Annex 1

Current BP and USP <1211> Monographs

5. Introduction

The sterility assurance for aseptic processing during final formulation and filling cannot be measured by the sterility test alone and therefore it is critical to routinely challenge the actual aseptic process under “worst case” conditions. Aseptic processing is challenged using microbiological growth media under simulated conditions.

The media fill is a simulation of the entire aseptic formulation and filling process, which substitutes a microbiological growth medium for a sterile product. The media fill also provides a way to evaluate changes made to aseptic processing operations which may affect the sterility assurance of the final product and the performance of aseptic filling personnel under operational conditions.

6. Pre-requisites for Aseptic Process Validation (Media Fills)

Before aseptic assembly or processing, different parts of the final product are generally subjected to different sterilisation processes, such as dry heat, moist heat, and sterile filtration.

Each stage of the aseptic filling operation requires validation and control as a pre-requisite to aseptic processing. Each also introduces the possibility of error that might ultimately lead to the distribution of contaminated product. Any manual or mechanical manipulation of the sterilised drug, components, containers, and closures prior to or during aseptic assembly poses a risk of contamination and thus necessitates careful control.

GMP facility ensures that a combination of full equipment qualification, component and equipment protection during handling and storage and rigorous personnel training are essential to the safe manufacture of aseptically manufactured products. 

Pre-requisites for Process Simulations

  • Critical areas (Grade B /Class 10,000 and Grade A / Class 100) are qualified and HVAC HEPA filters certified
  • Environmental monitoring procedures are qualified
  • Environmental monitoring media is approved for use
  • Validated equipment and component sterilisation steps are completed
  • Validated sterile filtration of bulk products is completed
  • Media used in simulations is qualified
  • Staff participating in the simulation are qualified in aseptic gowning
  • Staff entering the filling areas are trained in aseptic technique – includes filling operators, maintenance staff, QC staff and environmental monitoring staff.0