GXP

Matrix Approach for the Qualification of a Pharmaceutical Facility Autoclave

Introduction

While progress is being made with single-use sterile, disposable technology, autoclaves continue to be widely used in pharmaceutical facilities and they cannot be replaced completely. With steam sterilization there are two types of loads encountered in pharmaceutical manufacture: aqueous fluid loads in sealed containers (pharmaceutical preparations for terminal sterilization) and porous loads (items that may entrap air and inhibit the penetration of steam).   Porous load items include processing equipment (such as filling pumps), container-closures and filters.

Autoclaves function to eliminate microbial cells and endospores within a given device through the application of dry[J1] , saturated steam (1). Steam is assessed by a steam dryness fraction. This ratio is used to quantify the amount of water within steam. For example, if steam contains 10% water by mass, it is considered to be 90% dry (a dryness fraction of 0.9). ideally, with autoclave steam the aim is to have steam at close to 100% dryness. In doing so the autoclave acts as a pressure-cooker: water boils at 100°C, at atmospheric pressure, whereas at lower temperatures it boils at lower temperatures, at higher pressure it boils at higher temperatures.  At a steam over-pressure of one bar (or 100,000 Pascals), water boils at approximately 121°C. This allows the autoclave to produce temperatures above those that can ordinarily be achieved. Autoclaves commonly use saturated steam heated to between 115–134°C (250 - 273°F). To achieve a Sterility Assurance Level of 10-6 a holding time of at least 30 minutes at 115°C, 15 minutes at 121°C (250°F) or 3 minutes at 134°C (273°F) is required (2).

With steam sterilization devices the most critical functions are, arguably, the steam sterilization of direct and indirect the product contact parts. A second important aspect relates to air removal. All of the trapped air must be removed from the autoclave before activation. This is because trapped air is a very poor medium for achieving sterility. To be effective autoclaves and support systems need to be designed, installed, and qualified in a manner that ensures their continued reliability (3).

The validation and verification of the sterilization process requires careful planning, and this includes selection of the loads (pre-defined configurations of items to be sterilized). For the validation or qualification approach different strategies can be adopted. One such approach, which avoids the qualification of every load, is to adopt a matrix design (bracketing) approach where ‘worst case’ combinations for all of the intended loads can be selected. The matrix approach uses a philosophy which allows for the testing of a subset of the intended autoclave loads to validate the entire range of load, in lieu of testing each loads in the matrix. With this paper the focus is on non-liquid loads, although reference is made to alternative approaches than can be considered for liquid autoclave loads.  

 


 [J1]IT might be useful to describe what is meant by dry steam

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