Sterile Production

Understanding Sterile Production

VALIDATION OF ASEPTIC PROCESSES

PHARMACEUTICAL INSPECTION CONVENTION PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME 

4.1.3 It should be considered that inert gases will prevent the growth of aerobic microorganisms. Therefore for process simulations sterile filtered air should be used instead of inert gases, also for breaking a vacuum. Where anaerobes are detected in the environmental monitoring or sterility testing, the use of an inert gas should be considered for a process simulation, as inert gas is supporting the growth of anaerobes.  

VALIDATION OF ASEPTIC PROCESSES

PROCESS SIMULATION TEST PROCEDURES
4.1 General Comments

4.1.1 The media fill should emulate the regular product fill situation in terms of equipment, processes, personnel involved and time taken for filling as well as for holding.

4.1.2 Where filling takes place over extended periods, i.e. longer than 24 hours, the process simulation test should extend over the whole of the standard filling period. In order to prevent excessively high numbers of units being filled it is usually acceptable to just run the machine for a reasonable time, if the validity of the simulation is not diminished by this procedure.  

VALIDATION OF ASEPTIC PROCESSES -PIC/S

VALIDATION OF ASEPTIC PROCESSES 

It is the sum total of all validation data that provides the necessary level of assurance for aseptically produced products


Process simulation studies (media fills) are simulating the whole process in order to evaluate the sterility confidence of the process. Process simulation studies include formulation (compounding), filtration and filling with suitable media. Simulations are made to ensure that the regular process for commercial batches repeatedly and reliably produces the finished product of the required quality. However, each process simulation trial is unique and so it is not possible to extrapolate these results directly to actual production contamination rates.

VALIDATION OF ASEPTIC PROCESSES -PIC/S

PHARMACEUTICAL INSPECTION CONVENTION PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME

General information 2.3.1 The basic principles and application of process validation are described in Annex 15 to the EU/PIC/S Guide to GMP and are further elaborated in PIC/S Document PI 006 (Recommendations on Validation Master Plan, Installation and Operational Qualification, Non-Sterile Process Validation, Cleaning Validation) and apply also to aseptic processing. Annex I to the EU/ PIC/S Guide to GMP provides the basic requirements for the manufacture of sterile products including those aseptically processed. The Annex includes requirements, standards and recommendations, for example, for monitoring of the environment and of personnel.

.http://www.picscheme.org/pdf/26_pi007-6recommendationonasepticprocesses.pdf 

VALIDATION OF ASEPTIC PROCESSES -PIC/S

PHARMACEUTICAL INSPECTION CONVENTION PHARMACEUTICAL INSPECTION CO-OPERATION SCHEME

The aim of this document is to provide guidance to the current practice in this field by giving recommendations for the validation of aseptic processes. In particular, the document should provide guidance for GMP inspectors both for training purposes and in preparation for inspections of company premises

.http://www.picscheme.org/pdf/26_pi007-6recommendationonasepticprocesses.pdf