Great Expectations, Wrong Parameters

By failing to assess what is truly critical to safety, revised steam quality requirements fly in the face of common sense and a generation of sterilization science.

By James Agalloco, Agalloco & Associates

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The publication of HTM-2010 by the U.K.’s Medicines Inspection Agency in 1994 brought about a wholesale re-examination of steam sterilization across the global pharmaceutical industry [1]. While most of the documents in this lengthy tome offer greater insight into an important process, some have created tension and may lead to misunderstandings in a number of areas.

Inspectors, initially from just the U.K. but later from across Europe, began to assert the validity of “steam quality” to practitioners in the U.S. and elsewhere. An entire generation of sterilization scientists found their concepts and assumptions regarding sterilization effectiveness challenged by the precepts embodied in HTM-2010. Inquiries into non-condensable gases, moisture fraction, superheated steam and equilibration time resulted in difficulties when the exacting requirements of HTM-2010 were applied.

Resistance to the tenets of HTM-2010 has led to difficulties; facilities have been disapproved, processes altered and product changes and approvals have been delayed in order to promote conformance to the monograph. Voices raised in opposition have been somewhat placated by statements that the expectations apply only to porous load sterilization [2, 3].
 
Where sterilization of sealed containers is the concern, the “steam quality” concepts are acknowledged as irrelevant (many of these processes use air-over pressure to aid container-closure integrity during cooling of the load post-process, thus negating several of the key steam quality concerns). This has led to an unfortunate separation of thought. At the core of both schools of thought, processes, parts and terminal sterilization are the very same: moist heat destruction of microorganisms using saturated steam; and while the differences are seemingly substantial, there is commonality that if examined closely leads to clearer perspectives on porous load sterilization.

This article will re-examine revised steam quality expectations with full consideration of how steam sterilization is accomplished in settings other than porous loads.

Non-condensable Gases

A maximum of 3.5 mL of non-condensable gases per 100 mL of condensed steam is considered acceptable [1].

Revised steam quality expectations offer benefit in hospital settings, but little value to drug manufacturers.

At first glimpse, the notion that steam for sterilization should not contain gases that are not steam, and which could inhibit steam penetration to the surface of the object, seems eminently reasonable.

Consider, however, what occurs in a sealed sterile container of product with an air or nitrogen headspace. When an inoculum is applied to the underside of the stopper, and then subjected to the sterilization process (in the sealed container with heat supplied by steam on the outside of the container), the microorganisms are wholly inactivated provided there is steam contact with the surface where the microorganisms are placed (it is possible to inoculate where the stopper surface cannot be reached by the internally developed steam, in which case a moist heat resistant inoculum may survive). This occurs without any removal of air from the container and is in direct contrast with the expectation for minimal air in the moist heat process.

The situation inside the sealed container is similar to an autoclave without any air trap or condensate drain. The internal pressure in the headspace is higher than what would occur at equilibrium in a pure steam environment as a consequence of the non-condensable gases present in the container above the liquid surface. The absence of any gas removal from the container, accompanied with the destruction of the microorganisms internally, suggests that the presence of a substantial amount of non-condensable gases (as opposed to the minimal amounts tolerated by HTM-2010) has no adverse impact on the destruction of the microorganisms by moist heat. The notions of boundary layers and insulating effects of trace non-condensable gas on the sterilization process seem nonsensical in the face of complete kill without any air removal at all.

Moisture Fraction

The next “steam quality” element of concern is the potential presence of excessive moisture in the steam. The expectation here is that the steam will contain not more than 5% (10% for non-metallic loads) liquid in equilibrium with the gaseous steam [1]. This is somewhat counter-intuitive to begin with: the very first thing that happens with saturated steam when it contacts a cooler object is condensation of the steam vapor to liquid water. Placing a restrictive limit on this makes little sense given what will occur naturally in the autoclave when the steam contacts the load (as well as the walls of the sterilizer).

Returning to the terminal sterilization model, the absurdity of the requirement is even more evident. In terminal sterilization of liquids, the challenge microorganism is placed in the liquid (in addition to the container-closure area noted above that is evaluated separately).  Sterilization of solutions is readily accomplished where the moisture fraction is 100%, there being no steam present at all! The real effect of excessive moisture in saturated steam is to reduce the amount of heat available in the steam for heating the load elements to process temperature.

There is one more aspect of the moisture fraction that bears discussion. Moist heat sterilization derives its name from the presence of moisture in the heating process. Dry steam that does not condense during the sterilization process is no more effective than hot air in the sterilization of materials. Water must be present to attain sterilization in the 120°C to130°C range in the desired time period. Without liquid water, moist heat sterilization is impossible. A misnomer that seems all too common in this area is that of “dry saturated steam”. No such material exists in reality, as the most basic of requirements for saturation is the presence of both phases; liquid and gas.

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