Abstract
Steam sterilization is widely used across the healthcare industry and is the most documented and standardized sterilization method. Despite its broad application, there is considerable confusion regarding the different process control considerations and sterilizer designs necessary for its successful use. The methods and equipment used for porous loads (equipment, components, and tools) are established to address air removal and steam penetration as these are critical to process efficacy. Sterilizing processes and equipment for non-porous loads (sealed aqueous containers) seek to minimize variations across the load and minimize the potential for under- or over-processing of portions of the load. These distinctions are not always evident in publications. The United States Pharmacopeia content brought attention to these differences in General Chapter <1229.1> Sterilization by Direct Contact and General Chapter <1229.2> Moist Heat Sterilization of Aqueous Liquids. This publication provides expanded content beyond that found in USP in a side-by-side comparison of the process considerations and equipment design details. It also reviews sterilization practices in laboratory, formulation, and biowaste sterilization applications, which often require the simultaneous sterilization of porous and non-porous items.
- Steam sterilization
- Terminal sterilization
- Porous loads
- Non-porous loads
- Sterilizer design
- United States Pharmacopeia
Introduction
The origins of steam sterilization validation are found in the corrective actions taken in response to nearly simultaneous failures with terminal sterilization processes in the 1970s in the United States and the United Kingdom (1, 2). The immediate responses to these events were multiple and have had long-lasting impact. Validation practices have evolved substantially in the >40 years since those incidents. One problematic aspect that has emerged is that the dichotomy of process intent has made steam sterilization validation more complex than necessary. The difficulty results from forcing singular expectations on the differing equipment, process, and validation necessary to reliably sterilize load items with little in common other than using steam, either directly or indirectly, to sterilize them.
The differences began to emerge with the origin of sterilization validation practice. Failures with terminal sterilization prompted the first validation efforts and shaped the initial approaches used for all steam sterilization processes. When those charged with sterilization validation of nonterminal steam sterilization processes began their own efforts, they largely adopted practices identical to those for terminal sterilization as an expedient means of implementation. Over the intervening years, increasing sophistication in practice and more rigorous expectations brought forth added complexity in both terminal and nonterminal sterilization processes. At the same time, validation practices for the different processes became increasingly disparate within the industry, albeit with little acknowledgement in either regulations or standards. Although a singular approach is possible for sterilization of terminally sterilized products and sterilization of mechanical equipment, it is extremely wasteful of resources. Applying terminal sterilization requirements on porous load items adds unnecessary constraints on time–temperature, bioburden, and load configuration among others. Similarly, asserting parts sterilization practices on terminal loads added superfluous requirements for steam quality, air removal, and bioindicator choice.
The differences in moist heat sterilization derive from the different processes required to sterilize the variety of items whose surfaces must come into direct contact with the saturated steam, and sealed containers filled with aqueous liquids, where heating of the container exterior provides the means for internal sterilization of the contents. The differing means by which the varied items are to be sterilized establishes the specific process to be used, the equipment employed, and the cycle development/validation approach required.
The U.S. Pharmacopeia recognized the challenges the dichotomy of practice entailed early on during the redrafting of its sterilization-related content and provided for separation of moist heat sterilization content in its revised content (3, 4). This publication substantially expands upon the USP content and includes details on why moist heat sterilization should be considered two distinctly different processes. Parallel treatment of the numerous differences in process and equipment eases their comparison. Table I compares the sterilizer and sterilization processes performed within to highlight the differences in both.
Comparison of Sterilizers and Sterilization Processes
Other Steam Sterilization Usage
Although the major industrial use of steam sterilization is as outlined above, there are other steam sterilization processes that differ including: laboratory, manufacturing/formulation, and bio-decontamination. Each of these requires variations/adaptations to the practices for aqueous liquids and hard goods to accommodate the unique requirements presented by their usage.
Laboratory Sterilization Processes
These processes support sterility, environmental, bioburden, and material tests in which sterilization of the test apparatus and media is necessary. Many of these entail the simultaneous sterilization of both closed aqueous containers and heat-stable equipment. A parts sterilizer is customarily used to ensure penetration with slow exhaust to minimize physical stress on the liquid-filled containers. The aqueous media and buffer containers being sterilized commonly vary in size, contents, and configuration. The cycle duration must be limited so that media growth promotion is not impaired. Media sterilization is usually assessed by physical examination of the sterilized containers and the use of positive and negative controls in conjunction with each test. Depending upon the firm's policies, laboratory sterilization processes may or may not be validated. Laboratory sterilizers may also be used for sterilization of biological laboratory waste before disposal.
Commercial production of presterilized laboratory media in large volumes is performed and validated using terminal sterilization equipment/processes similar to those used for large volume parenterals (LVPs).
Manufacturing/Formulation Sterilization
The support of aseptic operations in compounding and formulation can require the sterilization of diverse items and this is customarily performed using direct exposure to steam following an overkill approach. If sterilization of an aqueous based fluid is required, adaptations may be necessary along the lines of those used in laboratory sterilizers. The key difference is that validation of this sterilization is required including evaluation of sterilization effects on the fluid. In many ways, sterilization in manufacturing mimics that of direct contact sterilization.
Bio-Decontamination
The destruction of biowaste materials (biosafety level [BSL]-3 and BSL-4) containing potentially hazardous microorganisms may be accomplished in a special autoclave design that prevents the discharge of condensate containing viable microorganisms (17). These sterilizers can simultaneously accommodate aqueous containers and hard goods. Because the goal is total elimination of contamination risk, only extreme overkill cycles are utilized. Validation of the bio-decontamination sterilization process is not a regulatory requirement, but it is well advised.
Multipurpose Sterilizers
Considering the preceding content, it might be concluded that steam sterilizers are fabricated for specific use. Although that approach affords optimum performance, many steam sterilizers are used for a variety of processes and materials. There are two prevailing means to realize operational flexibility with a single sterilizer design.
Porous Load Sterilizer for All Materials
This is an extremely common situation as the need for terminal sterilization capability may be minimal. Using a parts sterilizer for terminal sterilization results in significant compromises to the terminal process. Rapid cooling of the load is not possible in these sterilizers, effectively eliminating their use for heat-labile liquids. Some terminal sterilization-type capabilities can be easily accommodated: that is, air overpressure, F0 dwell control, and so forth. Sterilizers used in microbiology laboratories are the most common example of this approach.
Dual-Purpose Steam Sterilizers
It is possible to construct a steam sterilizer capable of both terminal and nonterminal usage. These units are both more complex and expensive; however, they are certainly less costly than two separate sterilizers. These hybrid designs may not provide performance comparable to sterilizers specific for a singular purpose.
Conclusion
The differences between the steam sterilization of aqueous containers and virtually all other items far outweigh the one similarity—that steam is used to heat the load. Although singular thinking could be applied, there is no benefit to doing so. Treating each process separately as described in USP <1229.1> and <1229.2> eases the execution of cycle development, validation, and routine operation of both processes. Respecting that these processes, and in many instances the equipment, have little real commonality makes perfect sense given the differing operational goals.
Conflict of Interest Declaration
The author declares that he has no competing interests.
- © PDA, Inc. 2020
