The old maxim that “an ounce of prevention is worth a pound of cure” certainly applies not only to the biopharmaceutical manufacturing industry but also to those other industries where high purity is an absolute requirement. The finished product is only as good as the ingredients and processes going into it, as well as the equipment that is used to create it. Many facilities choose a policy of removing rouge when it is spotted, while others prefer a riskier method of waiting until the rouge is detected in the systems . While the latter method theoretically minimizes the costs of maintenance by only addressing rouge when it becomes a problem, it is likely to be the more expensive option, and poses other risks related to more severe system corrosion.
By operating under the riskier option of delaying derouging until the contaminants appear in a batch, those operators have already calculated the lost cost of the contaminated product due to failing USP testing. They also take into account the estimated amount of time that the processing unit will be down for cleaning and remediation. However, those estimations are often “best scenario” and may not account for other issues that may be discovered during that servicing. Another hidden expense occurs in systems that rely on ultra-high purity water systems to feed the larger processing unit. Here the operator has made an investment in producing the purest water possible, with all the related operating costs, only to have all of that time, effort and expense negated by adding the water to a contaminated system.
The alternative to all of this is to take a science-based approach to derouging and passivation maintenance which allows the operator to turn such “known unknowns” into easily accountable and scheduled events.
Testing and Monitoring for Rouge
Waiting until rouge is detected carries a number of risks. First, the loss of the production batch due to contamination. But since rouge formation happens over an extended period, it means that recent previous batches may have also been contaminated, to just under the level that would lead to a rejection by USP testing. It’s also worth mentioning that rouge is most often generated within the production system itself. By waiting, it is likely the source area of the iron has experienced more severe degradation. Often, the iron forming the rouge is not coming directly from the failing component, but from a patch of iron crystals on the surface of the system somewhere upstream from where it was detected. These patches grow over time and the crystals will break off to be carried downstream within the process fluid. At this point, it is possible that the patches have also compromised the integrity of the stainless steel’s passive layer. This damage may require mechanical as well as chemical treatments to repair, adding to the expense of returning the unit back to service.
To avoid many of these risks, regular testing should be made of critical water or utilities and measuring oxide particles and soluble metals within them. The system should be designed so that filters and testing access points are placed throughout the process fluid system allowing them to be regularly monitored to detect where and when rouge forms. Additionally, there should be limit ranges for when maintenance must be performed to address the problem.
In fact, a monitoring protocol should be established to enable the detection of rouge at its earliest point. Such monitoring steps should include some or all of the following:
Developing a Visual Criteria
- Identifying the color and texture of the rouge can provide insight into the source of the free iron.
- Multiple inspection points allow personnel to more precisely identify where in the system the rouge is being formed, enabling the derouging to be more efficiently targeted.
Using Slipstream Filtration Data
- Monitoring the change in color of a filter over time allows for calculating the rate of rouge formation.
- Counting particles on the filter pad offers a way to quantify how much rouge is being formed.
- Inspecting the removable spool piece takes advantage of a purposely-designed, easily-removable piece of the system’s piping to visually inspect the condition of the interior of the piping in that area.
Analyze Water or Condensate for Contaminants
- Establishing the threshold level of iron or other contamination at which point the system must be taken out of service.
Testing the passive layer of the structural stainless steel can help determine a preventative derouging and passivation schedule. These options include using a Koslow passivation tester, an auger electron spectroscope, or an x-ray photoelectron spectroscope to help determine or rule out the stainless steel itself as the source of rouging.
Frequency of Derouging
A more proactive approach is to have scheduled derouging and passivation periods. Other work, including additional preventative maintenance, can also be performed during this scheduled downtime. The frequency of these scheduled outages varies upon the individual system. Water for Injection systems often require an annually scheduled service for derouging and passivation. Whereas, some systems, such as clean steam systems may be serviced at other intervals.
The quantitative data gathered from the monitoring protocol can be used to help create the preventative derouging and passivation maintenance schedule. By doing so, the operator can reduce the risk of rouge formation causing a work stoppage and unscheduled shut-down.
Once such a schedule is created, continuing with the monitoring protocols allows for data -based decisions on when to perform the services. The data can be used to set the limit ranges that may further adjust the schedule, such as after a period of a relatively heavy production surge. In such cases the preventative services may need to be modified, or an additional service scheduled in order to keep the system operating at full health.