The dryer was down. The product was contaminated. That’s what the operator called at 11 pm to say. When I got to the plant, the operator and I realized the culprit was the long-ignored steam sterilizer at the inlet to the spray dryer. The temperature profile showed the telltale sign of scaling; I reviewed the trends and discovered we had forgotten to pull the exchanger to remove the scale buildup on the steam side. I reminded maintenance also to remove the caramelized coating on the other side: non-uniformity can burn the product.
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Sterilization is an everyday practice at facilities subject to regulations governing production of pharmaceuticals and foods. Several metrics define performance. The probability that a single bacterium survived sterilization is expressed as the sterility assurance level (SAL). An SAL of 10-6 — also known as a “6th log reduction” — is the minimum acceptable probability in pharmaceuticals and foods. The “bioburden” is the opposite probability. However, there’s more to it: there must be enough cells to form a colony; a colony forming unit (CFU) could range from 70–1,200 cells. All methods of sterilization suffer from reliance on a method to determine bug survivability: usually they use a bacterium as this “biological indicator.”
Bugs just don’t roll over and die. A relationship between time and exposure expresses their resistance. A “D-value” defines the exposure time, in minutes, at a given dwell temperature to kill 90% of the organisms present. D-values intrinsically relate to conditions: temperature, humidity and chemical concentration. A “Z-value” is the temperature change required to reduce the bug population from 10 to one (log scale). It’s important to define a bracket of bug population versus time with divergent lines at maximum and minimum temperature. In simple terms, if the bioburden is 100 CFU, with a D-value of 0.7 min/log at 115°C, then the dwell time for a 6th log reduction is: log (100) + log (106)/0.7 = 11.4 min. There’s an equation to find equivalent kill time, Fo, at a different temperature: Fo = 10(T-T*)/Z-value where T is the new temperature and T* is the established temperature.
Pharmaceutical and food processors generally rely on clean-in-place (CIP) procedures. These fall into three categories: heat; chemical, e.g., ethylene oxide (EtO), nitrogen oxide, hydrogen peroxide, chlorine (Cl2) and ozone; and radiation. Plants tend to favor the latter two categories because they reduce contamination and damage; with gas methods like EtO, it’s easier to separate the product from the agent. Unfortunately, those two categories aren’t perfect. For instance, cardboard absorbs EtO and Cl2 forms toxic chloramines with ammonia in water while radiation hardens plastics and scrambles electronics. In addition, some chemicals pose a serious health and safety risk, as exemplified by the 2006 EtO explosion at Sterigenics. (For details on that incident, see the video made by the U.S. Chemical Safety Board) thickness
Dry heat, which kills by oxidizing the bacteria, sometimes is an option. However, it generally best suits wastes not production materials. Dry heat lacks the penetration capacity of wet heat.
You simply can’t beat the right kind of steam for sterilization. What is the right kind? A stream with 3–5% wet condensate will penetrate more effectively than dry steam, allowing a lower dwell temperature. Besides, wet steam has a better heat transfer coefficient.
What problems can you expect with steam sterilization? Well, obviously, scale buildup and caramelization; wet packing — allowing excess water to collect — probably because of steam trap failure; trapped air — vent the steam and air someplace; low temperature — often chosen to preserve products that are more difficult to maintain at temperature for the time needed to achieve sterilization; and, saving the worst for last, poor CIP practices — cleaning must remove the bulk of the waste in the pipe for sterilization to be effective.
Some equipment is especially difficult to clean and sterilize: filters, sample valves, thermowells, heat exchangers, centrifuges and pumps. So, it’s sensible to give special consideration during design and construction to avoiding the need for cleaning that involves disassembly, i.e., clean out of place (COP).
Most regulations offer some general guidelines but lack practical recommendations. May I suggest:
“Succeed at Steam Sterilization”
“Guidance for Industry”
“Aseptic Processing and Packaging…”
“USP Activities Impacting Sterilization…”
“Fo Value, D Value and Z Value Calculations”
