Using SOPs to deal with rouge
Rouge is often found during routine maintenance or visual inspections performed after cleaning. An inspection team needs a
clear definition of how to identify and document rouge and of whether this rouge has the potential to impact product quality
or not. These definitions should be provided in a standard operating procedure (SOP) to drive consistency, not only in reporting,
but in decisions to tag-out affected equipment, sample requirements, and in re-cleaning and investigative procedures to follow.
An SOP will give consistency not only to operators, but to QA and engineering activities as well. An SOP is a proactive way
the QA group can demonstrate the control and critical thinking needed to properly mitigate the impact of rouging on batches
of drug product. Performance of a risk assessment per ICH Q9 is a robust method of creating such an SOP.
An SOP should provide a simple, clear method of identifying, classifying, and determining the path forward. The procedure
should be pragmatic, and instructions for proceeding with maintenance and remediation or with processing should be clear for
anyone who may find visual anomalies on product contact equipment surfaces during the course of their work.
Different companies use numerous classifications of rouge, and many do nothing to help the operator or mechanic on the floor
define the problem or determine if it really is a problem. Saying that the rouge is "shiny and black" or "a glazed purple"
may help to identify the visual anomaly as rouge, but it does nothing to say if the material is additive to the process, or
if the spot of rouge on the side of the tank is rougher than the shiny stainless around the spot, which would indicate a more
difficult cleaning location. An SOP should use simple categories: one category should be for rouge that can impact a process
and requires an investigation and another category for rouge that does not. The SOP should include steps to determine the
category using visual criteria, roughness measuring, swabbing (i.e., a "wipe test"), or other straightforward methodology
to see whether the rouge is mobile or fixed and if it is cleanable. If the rouge is not additive, reactive, or absorptive,
and does not affect cleanability or operation, then it should be documented and processing should proceed. If the rouge is
additive or difficult to clean, it will impact the process and requires an investigation.
As-found conditions of tanks or valves that are opened only once each year or two should be documented and photographed. Any
problem found in such cases will impact every lot produced since the last inspection, so good documentation and rapid assessment
is crucial.
Good documentation practices that go along with routine maintenance or cleaning inspections will help the quality team build
a history of equipment or systems as well, allowing comparison over time and providing a window for product impact assessment.
An SOP can give the team clear guidance to perform their jobs correctly without outside assistance. The team should be trained
to document, evaluate, and then proceed with their sample collection or tag-out procedures as defined by the SOP.
Conclusion
Rouge has long been regularly seen in pharmaceutical plants, but very little consensus has been reached on pragmatic QA solutions.
QA personnel are not expected to be experts in the metallurgy of stainless steel, but must assure that equipment is in good
order, cleanable, and not contributing to contamination of products. Personnel should be able to assemble the data necessary
to assure this, quantify and qualify the risk based on knowledge of the products and equipment, and document the investigation
in a logical way. Implementing clear procedures will ensure that rouging does not paralyze operations and lot-release schedules.
John Anderson is validation manager at Lonza in Visp, Switzerland, johnnyred32@gmail.com
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References
1. R.W. Revie and H.H. Uhlig, "Iron and Steel," in Corrosion and Corrosion Control: An Introduction to Corrosion Science and Engineering, (John Wiley & Sons, Inc., Hoboken, NJ, 4th ed., 2008) pp. 115–148.
2. Code of Federal Regulations, Title 21, Food and Drugs (Government Printing Office, Washington, DC), Part 211.65(a)
3. T. Mathisen and J. Frantsen, Rouging of Stainless Steel in WFI Systems, Examples and Present Understandings, (Force Technology, Brondby, Denmark, 2007).
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